Exjade is an iron chelator indicated for the treatment of chronic iron overload due to blood transfusions in patients 2 years of age and older. This indication is based on reduction in serum ferritin and liver iron concentration (LIC). An improvement in survival or disease-related symptoms has not been established. (1.1)

Exjade is indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (NTDT) syndromes and with a 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. This indication is based on achievement of an LIC less than 5 mg Fe/g dw. An improvement in survival or disease-related symptoms has not been established. (1.2)

Limitation of Use
Controlled clinical trials of Exjade in patients with myelodysplastic syndromes (MDS) and chronic iron overload due to blood transfusion have not been performed. (1.3)

The safety and efficacy of Exjade when administered with other iron chelation therapy have not been established. (1.3)

• In patients with transfusional iron overload, the recommended initial daily dose is 20 mg per kg body weight once daily, as oral suspension. Calculate dose to the nearest whole tablet. (2.1)
• In patients with NTDT syndromes, the recommended initial daily dose is 10 mg per kg body weight once daily, as oral suspension. Calculate dose to the nearest whole tablet. (2.2)
• Monitor serum ferritin monthly and adjust dose accordingly. (2.1, 2.2)
• Monitor LIC every 6 months and adjust dose accordingly. (2.2)
• Do not chew or swallow tablets whole. (2.3)
• Take on an empty stomach at least 30 minutes before food. Disperse tablets by stirring in an appropriate amount of water, orange juice, or apple juice. (2.3)
• Reduce the starting dose in patients with moderate (Child-Pugh B) hepatic impairment by 50%. Avoid the use of Exjade in patients with severe (Child-Pugh C) hepatic impairment. (2.4)
• Reduce the starting dose by 50% in patients with renal impairment (ClCr 40-60 mL/min). (2.4)

Tablets for oral suspension: 125 mg, 250 mg, 500 mg. (3)

• Serum creatinine greater than 2 times the age-appropriate upper limit of normal or creatinine clearance less than 40 mL/min. (4)
• Patients with poor performance status. (4)
• Patients with high-risk myelodysplastic syndromes (MDS). (4)
• Patients with advanced malignancies. (4)
• Patients with platelet counts <50 x 109/L. (4)
• Known hypersensitivity to deferasirox or any component of Exjade. (4)

• Renal toxicity: Measure serum creatinine and creatinine clearance in duplicate before starting therapy. Monitor renal function during Exjade therapy and reduce dose or interrupt therapy for toxicity. (2.4, 5.1)
• Hepatic toxicity: Monitor hepatic function. Reduce dose or interrupt therapy for toxicity. (5.2)
• Fatal and nonfatal gastrointestinal bleeding, ulceration, and irritation: Risk may be greater in patients who are taking Exjade in combination with drugs that have known ulcerogenic or hemorrhagic potential. (5.3)
• Bone marrow suppression: Neutropenia, agranulocytosis, worsening anemia, and thrombocytopenia, including fatal events; monitor blood counts during Exjade therapy. Interrupt therapy for toxicity. (5.4)
• Elderly: Monitor closely for toxicity due to the greater frequency of decreased hepatic, renal, and/or cardiac function. (5.5)
• Serious and severe hypersensitivity reactions: Discontinue Exjade and institute medical intervention. (5.6)
• Severe skin reactions including Stevens Johnson Syndrome: Discontinue Exjade. (5.7)

In patients with transfusional iron overload, the most frequently occurring (>5%) adverse reactions are diarrhea, vomiting, nausea, abdominal pain, skin rashes, and increases in serum creatinine. In Exjade-treated patients with NTDT syndromes, the most frequently occurring (>5%) adverse reactions are diarrhea, rash and nausea. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Avoid the use of Exjade with aluminum-containing antacid preparations. (7.1)
• Exjade increases the exposure of the CYP2C8 substrate repaglinide. Consider repaglinide dose reduction and monitor blood glucose levels. (7.3)
• Avoid the use of Exjade with CYP1A2 substrate theophylline. (7.4)

• Pregnancy: Based on animal studies, may cause fetal harm. (8.1)
• Nursing Mothers: Discontinue drug or nursing, taking into consideration importance of drug to mother. (8.3)