Deferasirox Dosage

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Usual Adult Dose for:

Usual Pediatric Dose for:

Additional dosage information:

Usual Adult Dose for Iron Overload

Transfusional iron overload:

Initial Dose: 20 mg/kg once a day
Maintenance dose: 20 to 40 mg/kg/day
Maximum dose: 40 mg/kg/day

Comments: Doses should be rounded to the nearest whole tablet.

Usual Adult Dose for Thalassemia

Iron overload in non-transfusion dependent thalassemia syndromes:

Initial dose: 10 mg/kg orally once daily. Calculate doses (mg per kg per day) to the nearest whole tablet.

Comments: Deferasirox therapy should only be considered when a patient with a non-transfusion dependent thalassemia syndrome has a liver iron concentration (LIC) of at least 5 mg of iron per gram of liver dry weight (Fe/g dw) and a serum ferritin greater than 300 mcg/L.

Prior to starting therapy, obtain:
-LIC by liver biopsy or by an FDA-cleared or approved method for identifying patients for treatment with deferasirox therapy
-Serum ferritin level on at least 2 measurements one month apart
-Baseline serum creatinine in duplicate (due to variations in measurements) and determine the creatinine clearance (Cockcroft-Gault method)
-Serum transaminases and bilirubin
-Baseline auditory and ophthalmic examinations

Dose Adjustments:
-If the baseline LIC is greater than 15 mg Fe/g dw, consider increasing the dose to 20 mg/kg/day after 4 weeks.
-Monitor serum ferritin monthly.
-Interrupt treatment 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.
-Monitor LIC every 6 months.
-After 6 months of therapy, if the LIC remains greater than 7 mg Fe/g dw, increase the dose of deferasirox to a maximum of 20 mg/kg/day. Do not exceed a maximum of 20 mg/kg/day.
-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/day.
-When the LIC is less than 3 mg Fe/g dw, interrupt treatment with deferasirox and continue to monitor the LIC.
-Monitor blood counts, hepatic function, and renal function.
-Restart treatment when the LIC rises again to more than 5 mg Fe/g dw.

Usual Pediatric Dose for Iron Overload

Transfusional iron overload:
2 years of age or older:

Initial Dose: 20 mg/kg once a day
Maintenance dose: 20 to 40 mg/kg/day
Maximum dose: 40 mg/kg/day

Comments: Doses should be rounded to the nearest whole tablet.

Usual Pediatric Dose for Thalassemia

In patients 10 years of age and older for treatment of chronic iron overload in non-transfusion dependent thalassemia syndromes:

Initial dose: 10 mg/kg orally once daily. Calculate doses (mg per kg per day) to the nearest whole tablet.

Comments: Deferasirox therapy should only be considered when a patient with a non-transfusion dependent thalassemia syndrome has a liver iron concentration (LIC) of at least 5 mg of iron per gram of liver dry weight (Fe/g dw) and a serum ferritin greater than 300 mcg/L.

Prior to starting therapy, obtain:
-LIC by liver biopsy or by an FDA-cleared or approved method for identifying patients for treatment with deferasirox therapy
-Serum ferritin level on at least 2 measurements one month apart
-Baseline serum creatinine in duplicate (due to variations in measurements) and determine the creatinine clearance (Cockcroft-Gault method)
-Serum transaminases and bilirubin
-Baseline auditory and ophthalmic examinations

Dose Adjustments:
-If the baseline LIC is greater than 15 mg Fe/g dw, consider increasing the dose to 20 mg/kg/day after 4 weeks.
-Monitor serum ferritin monthly.
-Interrupt treatment 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.
-Monitor LIC every 6 months.
-After 6 months of therapy, if the LIC remains greater than 7 mg Fe/g dw, increase the dose of deferasirox to a maximum of 20 mg/kg/day. Do not exceed a maximum of 20 mg/kg/day.
-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/day.
-When the LIC is less than 3 mg Fe/g dw, interrupt treatment with deferasirox and continue to monitor the LIC.
-Monitor blood counts, hepatic function, and renal function.
-Restart treatment when the LIC rises again to more than 5 mg Fe/g dw.

Renal Dose Adjustments

Baseline Renal Impairment:
CrCl 40 to 60 mL/min: Reduce the starting dose by 50%.
CrCl less than 40 mL/min or serum creatinine greater than 2 times ULN: Do not use deferasirox.

Dose adjustments for increases in serum creatinine while on deferasirox:
Transfusional Iron Overload:
Adults and Adolescents (age 16 and older):
If the serum creatinine increases 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 per kg.

Pediatric Patients (ages 2-15 years):
Reduce the dose by 10 mg per kg if serum creatinine increases to greater than 33% above the average baseline measurement and is greater than the age appropriate upper limit of normal.

All Patients (regardless of age):
Discontinue therapy for serum creatinine greater than 2 times the age-appropriate upper limit of
normal or for creatinine clearance less than 40 mL/min.

Non-Transfusion Dependent Thalassemia Syndromes:
Adults and Adolescents (ages 16 and older):
If the serum creatinine increases 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 per kg, or reduce by 50% if the dose is 10 or 20 mg per kg.

Pediatric Patients (ages 10-15 years):
Reduce the dose by 5 mg per kg if serum creatinine increases to greater than 33% above the average baseline measurement and greater than the age appropriate upper limit of normal.

All Patients (regardless of age):
Discontinue therapy for serum creatinine greater than 2 times the age-appropriate upper limit of normal or for creatinine clearance less than 40 mL/min.

Liver Dose Adjustments

Mild (Child-Pugh A) hepatic impairment: No dose adjustment is necessary.
Moderate (Child-Pugh B) hepatic impairment: Reduce the starting dose by 50%.
Severe (Child-Pugh C) hepatic impairment: Avoid deferasirox use.

Dose Adjustments

Transfusional iron overload:
After commencing initial therapy, serum ferritin should be monitored every month and the dose of deferasirox should be adjusted if necessary every 3 to 6 months based on serum ferritin trends. Dose adjustments may occur in steps of 5 or 10 mg/kg and tailored to the individual patient's response and therapeutic goals (maintenance or reduction of body iron burden). In patients not adequately controlled with doses of 30 mg/kg (e.g., serum ferritin levels persistently above 2500 mcg/L and not showing a decreasing trend over time), doses of up to 40 mg/kg may be considered. Doses above 40 mg/kg are not recommended.

If the serum ferritin falls consistently below 500 mcg/L, temporary interruption of therapy with deferasirox should be considered.

The risk of toxicity of deferasirox may be increased when inappropriately high doses are given in patients with low iron burden or with serum ferritin levels that are only slightly elevated. The safety and efficacy of deferasirox when administered with other iron chelation therapy have not been established.

In cases where skin rash is severe, deferasirox therapy may be interrupted. Reintroduction at a lower dose with escalation may be considered in combination with a short period of oral steroid administration.

Precautions

Deferasirox therapy requires close patient monitoring, including serum creatinine and/or creatinine clearance prior to initiation of therapy and monthly thereafter. In patients with underlying renal impairment or risk factors for renal impairment, creatinine and/or creatinine clearance should be monitored weekly for the first month, then monthly thereafter.

Transaminases and bilirubin should be monitored before the initiation of treatment, every two weeks during the first month and monthly thereafter. Consider dose modifications or interruption of treatment for severe or persistent elevations.

Prior to starting therapy, obtain baseline serum ferritin and iron levels. The risk for toxicity may be increased when deferasirox is given to patients with low iron burden or with serum ferritin levels that are only slightly elevated.

Physicians and patients should remain alert for signs and symptoms of gastrointestinal ulceration and hemorrhage during deferasirox therapy and promptly initiate additional evaluation and treatment if a serious gastrointestinal adverse event is suspected.

Auditory and ophthalmic testing (including slit lamp examinations and dilated fundoscopy) are recommended before starting deferasirox treatment and thereafter at regular intervals (every 12 months). If disturbances are noted, consider dose reduction or interruption.

Dialysis

Data not available

Other Comments

Administration advice:
-Deferasirox should be taken on an empty stomach at least 30 minutes before food and preferably at the same time each day.
-Tablets should not be chewed or swallowed whole. Tablets should be completely dispersed by stirring in water, orange juice, or apple juice until a fine suspension is obtained. Doses less than 1,000 mg should be dispensed in 3.5 ounces of liquid and doses greater than 1,000 mg should be dispensed in seven ounce of liquid.

Storage requirements: Protect from moisture

Patient advice:
-Deferasirox should not be taken with aluminum-containing antacid products.
-Although deferasirox has a very low affinity for zinc and copper, there are variable decreases in the serum concentration of these trace metals after the administration of deferasirox. The clinical significance of these decreases is uncertain.

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