Deferasirox

Brand Names: Deferasirox

Drug Class: Iron Chelator

Overview

11 DESCRIPTION Deferasirox is an iron-chelating agent provided as a tablet for oral use. Deferasirox is designated chemically as 4-[3,5-bis(2-hydroxy-phenyl)-1 H -1,2,4-triazol-1-yl] benzoic acid and has the following structural formula: Deferasirox is a white to slightly yellow colour powder. It has a molecular formula C 21 H 15 N 3 O 4 and molecular weight of 373.36.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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. 12.2 Pharmacodynamics Pharmacodynamic effects tested in an iron balance metabolic study with the tablet for oral suspension formulation showed that deferasirox (10, 20, and 40 mg per kg per day) was able to induce a mean net iron excretion (0.119, 0.329, and 0.445 mg Fe/kg body weight per day, respectively) within the clinically relevant range (0.

Indications

  • 1 INDICATIONS AND USAGE Deferasirox tablets are an iron chelator indicated for the treatment of chronic iron overload due to blood transfusions in patients 2 years of age and older. ( 1.1 ) Deferasirox tablets are 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 (Fe/g dw) and a serum ferritin greater than 300 mcg/L.( 1.

Common Doses

  • 60 mL
  • 14 mg
  • 7 mg
  • 100 mL

Dosage

2 DOSAGE AND ADMINISTRATION Transfusional Iron Overload: Initial dose for patients with estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1.73 m 2 is 14 mg per kg (calculated to nearest whole tablet ) once daily. ( 2.1 ) NTDT Syndromes: Initial dose for patients with eGFR greater than 60 mL/min/1.73 m 2 is 7 mg per kg (calculated to nearest whole tablet) once daily. ( 2.2 ) See full prescribing information for information regarding monitoring, administration, and dose-reductions for organ impairment. ( 2.1 , 2,2 , 2.3 , 2.4 ) 2.

Black Box Warning

WARNING: RENAL FAILURE, HEPATIC FAILURE, and GASTROINTESTINAL HEMORRHAGE Renal Failure Deferasirox 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 deferasirox dosing in all patients. Deferasirox is contraindicated in adult and pediatric patients with eGFR less than 40 mL/min/1.73 m 2 . Measure serum creatinine in duplicate prior to initiation of therapy. Monitor renal function at least monthly.

Contraindications

  • 4 CONTRAINDICATIONS Deferasirox is contraindicated in patients with: Estimated GFR less than 40 mL/min/1.73 m 2 [see Dosage and Administration (2.5) , Warnings and Precautions (5.1) ]; Poor performance status [see Warnings and Precautions ( 5.1, 5.3 )]; High-risk myelodysplastic syndromes (this patient population was not studied and is not expected to benefit from chelation therapy); Advanced malignancies [see Warnings and Precautions ( 5.1, 5.3 )]; Platelet counts less than 50 x 10 9 /L [see Warnings and Precautions ( 5.3 , 5.

Side Effects

  • 6 ADVERSE REACTIONS 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 [ see Warnings and Precautions (5.1,5.6)] Hepatic Toxicity and Failure [ see Warnings and Precautions (5.2,5.6)] GI Hemorrhage [ see Warnings and Precautions (5.3 )] Bone Marrow Suppression [ see Warnings and Precautions (5.4)] Hypersensitivity [see Warnings and Precautions (5.7) ] Severe Skin Reactions [see Warnings and Precautions (5.

Interactions

  • 7 DRUG INTERACTIONS Do not take deferasirox with aluminum-containing antacid preparations.( 7.1 ) Deferasirox increases the exposure of the repaglinide. Consider repaglinide dose reduction and monitor blood glucose levels. ( 7.3 ) Avoid the use of deferasirox with theophylline as theophylline levels could be increased. ( 7.4 ) Deferasirox increases exposure of busulfan. Monitor plasma concentrations of busulfan when coadministered with deferasirox to allow dose adjustment of busulfan, as needed. ( 7.7 ) 7.