Deferasirox

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. 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. Limitations of Use: The safety and efficacy of Exjade when administered with other iron chelation therapy have not been established.

Exjade (deferasirox) is an orally active chelator that is selective for iron (as Fe 3+ ). It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio. Although deferasirox has 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.

Transfusional Iron Overload: Initial dose for patients with estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1.73 m 2 is 20 mg per kg body weight once daily, as oral suspension. Calculate dose to the nearest whole tablet. NTDT Syndromes: Initial dose for patients with eGFR greater than 60 mL/min/1.73 m 2 is 10 mg per kg body weight once daily, as oral suspension.

Exjade is contraindicated in patients with: Estimated GFR less than 40 mL/min/1.73 m 2, Poor performance status, High-risk myelodysplastic syndromes, (this patient population was not studied and is not expected to benefit from chelation therapy) Advanced malignancies. Platelet counts less than 50 x 10 9 /L. Estimated GFR less than 40 mL/min/1.73 m 2. Patients with poor performance status. Patients with high-risk myelodysplastic syndrome (MDS). Patients with advanced malignancies. Patients with platelet counts less than 50 x 10 9 /L. Known hypersensitivity to deferasirox or any component of Exjade.

Boxed warning (renal failure, hepatic failure, and gastrointestinal hemorrhage): Renal Failure Exjade 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 Exjade dosing in all patients. Acute Kidney Injury: Measure serum creatinine in duplicate before starting therapy. Monitor renal function during Exjade therapy and reduce dose or interrupt therapy for toxicity. Hepatic Toxicity: Monitor hepatic function. Reduce dose or interrupt therapy for toxicity. 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.

The following clinically significant adverse reactions are also discussed in other sections of the labeling: Acute Kidney Injury, Including Acute Renal Failure Requiring Dialysis, and Renal Tubular Toxicity Including Fanconi Syndrome Hepatic Toxicity and Failure GI Hemorrhage Bone Marrow Suppression Hypersensitivity Severe Skin Reactions Skin Rash Auditory and Ocular Abnormalities In patients with transfusional iron overload, the most frequently occurring (greater than 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 (greater than 5%) adverse reactions are diarrhea, rash, and nausea.

Do not take Exjade with aluminum-containing antacid preparations. Exjade increases the exposure of the CYP2C8 substrate repaglinide. Consider repaglinide dose reduction and monitor blood glucose levels. Avoid the use of Exjade with CYP1A2 substrate theophylline. Deferasirox increases exposure of busulfan. Monitor plasma concentrations of busulfan when coadministered with deferasirox to allow dose adjustment of busulfan as needed.

Store Exjade tablets at 20°C to 25°C (68°F to 77°F), excursions are permitted between 15°C to 30°C (59°F to 86°F). Protect from moisture.