Usual Adult Dose for Iron Overload

Exjade(R):
Initial dose: 20 mg/kg, orally, once a day - calculate dose to the nearest whole tablet
Monitor serum ferritin monthly: Adjust dose every 3 to 6 months, by 5 to 10 mg/kg, based on serum ferritin trends
Maximum dose: 40 mg/kg

Jadenu(R):
Initial dose: 14 mg/kg, orally, once a day - calculate dose to the nearest whole tablet
Monitor serum ferritin monthly: Adjust dose every 3 to 6 months, by 3.5 to 7 mg/kg, based on serum ferritin trends
Maximum dose: 28 mg/kg

Comments:

• Only consider therapy when evidence of chronic transfusional overload exists (e.g. transfusion of at least 100 mL/kg packed red blood cells and a serum ferritin consistently greater than 1000 mcg/L).
• Prior to treatment, obtain serum ferritin level, baseline serum creatinine in duplicate and determine creatinine clearance, serum transaminases, bilirubin, and baseline auditory and ophthalmic examinations.
• Tailor dose to patient response and therapeutic goals.

Use: Transfusional iron overload

Usual Adult Dose for Thalassemia

Exjade(R):
Initial dose: 10 mg/kg, orally, once a day - calculate dose to the nearest whole tablet

• If baseline liver iron concentration (LIC) is over 15 Fe/g dw, consider increasing dose to 20 mg/kg/day after 4 weeks

Maximum dose: 20 mg/kg/day

After 6 months therapy:

• If LIC remains above 7 mg Fe/g dw: increase to 20 mg/kg/day
• If LIC is 3 to 7 mg Fe/g dw: Continue at no more than 10 mg/kg/day

Jadenu(R):
Initial dose: 10 mg/kg, orally, once a day - calculate dose to the nearest whole tablet

• If baseline liver iron concentration (LIC) is over 15 Fe/g dw, consider increasing dose to 14 mg/kg/day after 4 weeks

Maximum dose: 14 mg/kg

After 6 months therapy:

• If LIC remains above 7 mg Fe/g dw: increase to 14 mg/kd/day
• If LIC is 3 to 7 mg Fe/g dw: Continue at no more than 7 mg/kg/day

Exjade(R) and Jadenu(R):
Monitor serum ferritin monthly:

• Serum ferritin under 300 mcg/L: Interrupt treatment and determine if LIC has fallen to less than 3 mg Fe/g dw.

If LIC is less than 3 mg Fe/g dw: Interrupt treatment and continue to monitor LIC

• Restart treatment when LIC rises to 5 mg Fe/g dw or higher.

Comments:

• Only consider therapy for liver iron concentration (LIC) of at least 5 mg Fe/g dw and a serum ferritin over 300 mcg/L.
• Prior to treatment, obtain LIC by liver biopsy or other approved method, serum ferritin level, baseline serum creatinine in duplicate and determine creatinine clearance, serum transaminases, bilirubin, and baseline auditory and ophthalmic examinations.
• Monitor LIC every 6 months.
• Monitor blood counts, hepatic function, and renal function.

Use: Chronic iron overload in non-transfusion dependent thalassemia syndromes

Usual Pediatric Dose for Iron Overload

Exjade(R) - 2 years and older:
Initial dose: 20 mg/kg, orally, once a day - calculate dose to the nearest whole tablet
Monitor serum ferritin monthly: Adjust dose every 3 to 6 months, by 5 to 10 mg/kg, based on serum ferritin trends
Maximum dose: 40 mg/kg

Jadenu(R) - 2 years and older:
Initial dose: 14 mg/kg, orally, once a day - calculate dose to the nearest whole tablet
Monitor serum ferritin monthly: Adjust dose every 3 to 6 months, by 3.5 to 7 mg/kg, based on serum ferritin trends
Maximum dose: 28 mg/kg

Comments:

• Only consider therapy when evidence of chronic transfusional overload exists (e.g. transfusion of at least 100 mL/kg packed red blood cells and a serum ferritin consistently greater than 1000 mcg/L).
• Prior to treatment, obtain serum ferritin level, baseline serum creatinine in duplicate and determine creatinine clearance, serum transaminases, bilirubin, and baseline auditory and ophthalmic examinations.
• Tailor dose to patient response and therapeutic goals.

Use: Transfusional iron overload

Usual Pediatric Dose for Thalassemia

Exjade(R):
10 years and older:
Initial dose: 10 mg/kg, orally, once a day - calculate dose to the nearest whole tablet

• If baseline liver iron concentration (LIC) is over 15 Fe/g dw, consider increasing dose to 20 mg/kg/day after 4 weeks

Maximum dose: 20 mg/kg/day

After 6 months therapy:

• If LIC remains above 7 mg Fe/g dw: increase to 20 mg/kg/day
• If LIC is 3 to 7 mg Fe/g dw: Continue at no more than 10 mg/kg/day

Jadenu(R):
10 years and older:
Initial dose: 10 mg/kg, orally, once a day - calculate dose to the nearest whole tablet

• If baseline liver iron concentration (LIC) is over 15 Fe/g dw, consider increasing dose to 14 mg/kg/day after 4 weeks

Maximum dose: 14 mg/kg

After 6 months therapy:

• If LIC remains above 7 mg Fe/g dw: increase to 14 mg/kg/day
• If LIC is 3 to 7 mg Fe/g dw: Continue at no more than 7 mg/kg/day

Exjade(R) and Jadenu(R):
Monitor serum ferritin monthly:

• Serum ferritin under 300 mcg/L: Interrupt treatment and determine if LIC has fallen to less than 3 mg Fe/g dw.

If LIC is less than 3 mg Fe/g dw: Interrupt treatment and continue to monitor LIC

• Restart treatment when LIC rises to 5 mg Fe/g dw or higher.

Comments:

• Only consider therapy for liver iron concentration (LIC) of at least 5 mg Fe/g dw and a serum ferritin over 300 mcg/L.
• Prior to treatment, obtain LIC by liver biopsy or other approved method, serum ferritin level, baseline serum creatinine in duplicate and determine creatinine clearance, serum transaminases, bilirubin, and baseline auditory and ophthalmic examinations.
• Monitor LIC every 6 months.
• Monitor blood counts, hepatic function, and renal function.

Use: Chronic iron overload in non-transfusion dependent thalassemia syndromes

Renal Dose Adjustments

Contraindicated if estimated glomerular filtration rate (eGFR) is less than 40 mL/min/1.73 m2

Creatinine clearance 40 to 60 mL/min or eGFR 40 to 60 mL/min/1.73 m2:

• Reduce starting dose by 50%, closely monitor serum creatinine and creatinine clearance.
• Reduce, interrupt, or discontinue based on increases in serum creatinine.
• Use caution in pediatric patients with eGFR of 40 to 60 mL/min/1.73 m2; use the minimum effective dose and enhance monitoring of glomerular or renal tube functioning (or both) to avoid acute renal failure.
• Monitor all patients closely for changes in eGFR and renal tubular dysfunction during treatment; consider dose reduction, interruption, or discontinuation until glomerular or renal tubular function returns to normal.

Creatinine clearance under 40 mL/min or serum creatinine more than twice the upper limit of normal: Contraindicated

Comments:
Closely monitor for efficacy and adverse reactions that may require dose titration.

Liver Dose Adjustments

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

Comments:
Closely monitor for efficacy and adverse reactions that may require dose titration.

Dose Adjustments

Transfusional Iron Overload Dose Adjustments:

• Patients not adequately controlled at 30 mg/kg (e.g. serum ferritin persistently above 2500 mcg/L with no decreasing trend):
• Exjade(R): Doses up to 40 mg/kg may be considered.
• Jadenu(R): Doses up to 28 mg/kg may be considered.
• Serum ferritin falling consistently below 500 mcg/L: Consider temporary interruption of therapy

Transfusional Iron Overload - Serum Creatinine Increases:

• Reduce Exjade(R) dose by 10 mg/kg or Jadenu(R) dose by 7 mg/kg if:
• 16 years and older: If serum creatinine increases 33% or more over baseline, repeat serum creatinine within 1 week; if still elevated 33% or more, reduce dose.
• 2 to 15 years: Reduce dose if serum creatinine increases 33% or more over baseline, or is greater than the upper limit of normal.
• Discontinue therapy if serum creatinine is twice the upper limit of normal, or for creatinine clearance under 40 mL/min (all ages).

Thalassemia - Serum Creatinine Increases:

• 16 years and older: If serum creatinine increases 33% or more over baseline, repeat serum creatinine within 1 week; if still elevated 33% or more, reduce dose by half if patient is on 10 to 20 mg/kg for Exjade(R) or 7 to 14 mg/kg for Jadenu(R); interrupt therapy if dose is 5 mg/kg for Exjade(R) or 3.5 mg/kg for Jadenu(R).
• 10 to 15 years: Serum creatinine increases 33% or more over baseline, or is greater than the upper limit of normal: Reduce dose by 5 mg/kg for Exjade(R) or 3.5 mg/kg for Jadenu(R).
• Discontinue therapy if serum creatinine is twice the upper limit of normal, or for creatinine clearance under 40 mL/min (all ages).

Use with Concomitant Medications (Exjade(R) and Jadenu(R)):

UDP-glucuronosyltransferases (UGT) Inducers e.g. rifampin, phenytoin, phenobarbital, ritonavir)
OR
Bile Acid Sequestrants (e.g. cholestyramine, colesevelam, colestipol):

• Avoid concomitant use; these medications decrease exposure to deferasirox.
• If co-administration cannot be avoided, consider increasing the initial dose of deferasirox by 50%; monitor serum ferritin and clinical response for further dose modification.

Precautions

US BOXED WARNINGS:
RENAL FAILURE:

• This drug can cause acute renal failure and death, particularly in patients with comorbidities and those who are in the advanced stages of their hematologic disorders
• Evaluate baseline renal function prior to starting or increasing dose in all patients.
• Measure serum creatinine and determine creatinine clearance in duplicate prior to therapy initiation; monitor renal function at least monthly thereafter.
• For patients with baseline renal impairment or increased risk of acute renal failure, monitor renal function, including creatinine weekly for the first month, and then at least monthly thereafter.
• Reduce the starting dose in patients with preexisting renal disease.
• During therapy, increase monitoring frequency and modify dose for those at increased risk of renal impairment, including those on concomitant nephrotoxic drugs, and pediatric patients with volume depletion or overchelation.
• Consider dose reduction, interruption, or discontinuation based on increases in serum creatinine.

HEPATIC FAILURE:

• This drug can cause hepatic failure and death.
• Measure serum transaminases and bilirubin in all patients prior to therapy initiation, every 2 weeks for the first month, then at least monthly thereafter.
• Avoid use in severe hepatic impairment (Child-Pugh C); reduce dose in moderate hepatic impairment (Child-Pugh B).

GASTROINTESTINAL HEMORRHAGE:

• This drug can cause gastrointestinal (GI) hemorrhages, which may be fatal, especially in elderly patients with advanced hematologic malignancies and/or low platelet counts.
• Monitor patients and discontinue for suspected GI ulceration or hemorrhage.

Safety and efficacy have not been established in patients younger than 2 years for transfusional iron overload or 10 years for non-transfusion dependent thalassemia.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Take once daily on an empty stomach or with a light meal, preferably at the same time each day.
• Swallow tablets with water or other liquids.
• Patients who have difficulty swallowing the whole tablets may crush them and mix with soft foods (e.g. yogurt or apple sauce) immediately prior to use; do not store for future use.
• Advise against use of commercial crushers with serrated surfaces for crushing single 90 mg tablets.
• The sprinkles/granules formulation should be sprinkled on soft food (e.g. yogurt or apple sauce) immediately prior to use.
• Do not take with aluminum containing antacids.

Storage requirements:

• Store at room temperature.

Patient advice:

• Advise patients there will be frequent blood tests to check for damage to kidneys, liver, or blood cells.
• Caution patients about the potential to develop GI ulcers or bleeding when combined with drugs with ulcerogenic or hemorrhagic potential, such as NSAIDs, corticosteroids, oral bisphosphonates, or anticoagulants.
• Skin rashes may occur and may interrupt treatment if severe.
• Serious allergic reactions, including swelling of the throat, have been reported, usually within the first month of treatment; advise patients to stop taking this drug for severe reactions and to contact their doctor immediately.
• Auditory and ocular testing should be done at baseline and regularly during treatment, as auditory and ocular disturbances have been reported.