Transfusional Iron Overload

The safety and effectiveness of deferasirox have been established in pediatric patients 2 years of age and older for the treatment of transfusional iron overload [see Dosage and Administration (2.1)].

Safety and effectiveness have not been established in pediatric patients less than 2 years of age for the treatment of transfusional iron overload.

Pediatric approval for treatment of transfusional iron overload was based on clinical studies of 292 pediatric patients 2 years to less than 16 years of age with various congenital and acquired anemias. Seventy percent of these patients had beta-thalassemia [see Indications and Usage (1), Dosage and Administration (2.1), Clinical Studies (14)]. In those clinical studies, 173 children (ages 2 to < 12 years) and 119 adolescents (ages 12 to < 17 years) were exposed to deferasirox.

A trial conducted in treatment-naïve pediatric patients, 2 to < 18 years of age with transfusional iron overload (NCT02435212) did not provide additional relevant information about the safety or effectiveness of the deferasirox granules dosage form (Jadenu Sprinkle) compared to the deferasirox oral tablets for suspension dosage form.

Iron Overload in Non-Transfusion-Dependent Thalassemia Syndromes

The safety and effectiveness of deferasirox have been established in patients 10 years of age and older for the treatment of chronic iron overload with non-transfusion-dependent thalassemia (NTDT) syndromes [see Dosage and Administration (2.2)].

Safety and effectiveness have not been established in patients less than 10 years of age with chronic iron overload in NTDT syndromes.

Pediatric approval for treatment of NTDT syndromes with liver iron (Fe) concentration (LIC) of at least 5 mg Fe per gram of dry weight and a serum ferritin greater than 300 mcg/L was based on 16 pediatric patients treated with deferasirox therapy (10 years to less than 16 years of age) with chronic iron overload and NTDT. Use of deferasirox in these age groups is supported by evidence from adequate and well-controlled studies of deferasirox in adult and pediatric patients [see Indications and Usage (1.2), Dosage and Administration (2.2), Clinical Studies (14)].

In general, risk factors for deferasirox-associated kidney injury include preexisting renal disease, volume depletion, overchelation, and concomitant use of other nephrotoxic drugs. Acute kidney injury, and acute liver injury and failure has occurred in pediatric patients. In a pooled safety analysis, pediatric patients with higher deferasirox exposures had a greater probability of renal toxicity and decreased renal function, resulting in increased deferasirox exposure and progressive renal toxicity/kidney injury. Higher rates of renal adverse reactions have been identified among pediatric patients receiving deferasirox doses greater than 25 mg/kg/day when their serum ferritin values were less than 1,000 mcg/L [see Dosage and Administration (Error! Hyperlink reference not valid.), Warnings and Precautions (Error! Hyperlink reference not valid., Error! Hyperlink reference not valid.), Adverse Reactions (Error! Hyperlink reference not valid., Error! Hyperlink reference not valid.)]. 

Monitoring Recommendations for pediatric patients with Transfusional Iron Overload and NTDT It is recommended that serum ferritin be monitored every month to assess the patient’s response to therapy and to minimize the risk of overchelation [see Warnings and Precautions (5.6)].

Monitor renal function by estimating GFR using an eGFR prediction equation appropriate for pediatric patients and evaluate renal tubular function. Monitor renal function more frequently in pediatric patients in the presence of renal toxicity risk factors, including episodes of dehydration, fever and acute illness that may result in volume depletion or decreased renal perfusion. Use the minimum effective dose [see Warnings and Precautions (Error! Hyperlink reference not valid.)]. 

Interrupt deferasirox in pediatric patients with transfusional iron overload and consider dose interruption in pediatric patients with non-transfusion-dependent iron overload, for acute illnesses, which can cause volume depletion, such as vomiting, diarrhea, or prolonged decreased oral intake, and monitor more frequently. Resume therapy as appropriate, based on assessments of renal function, when oral intake and volume status are normal. Evaluate the risk benefit profile of continued deferasirox use in the setting of decreased renal function. Avoid use of other nephrotoxic drugs [see Dosage and Administration (Error! Hyperlink reference not valid.), Warnings and Precautions (Error! Hyperlink reference not valid.)].

Juvenile Animal Toxicity Data 

Renal toxicity was observed in adult mice, rats, and marmoset monkeys administered deferasirox at therapeutic doses. In a neonatal and juvenile toxicity study in rats, deferasirox was administered orally from postpartum Day 7 through 70, which equates to a human age range of term neonate through adolescence. Increased renal toxicity was identified in juvenile rats compared to adult rats at a dose based on mg/m2 approximately 0.4 times the recommended dose of 20 mg/kg/day. A higher frequency of renal abnormalities was noted when deferasirox was administered to non-iron overloaded animals compared to iron overloaded animals.