Exjade (Deferasirox)

Introduction

In transfusion-dependent thalassemia, lifelong blood transfusions is the mainstay treatment for most patients. However, chronic iron overload may occur as a complication of multiple blood transfusions. On the other hand, individuals with transfusion-independent thalassemia accumulate iron due to increased absorption of dietary iron rather than via repeated blood transfusions.

The goal of iron chelation therapy is to reduce the body burden of iron, especially iron within labile compartments in plasma as well as in various tissues. By decreasing iron in these sites, it minimizes the production of reactive oxygen species, thus reducing damage to critical organs such as liver, heart and endocrine organs, resulting in reduced morbidity and improved survival.

There are several options for initial chelating therapy:

  • Deferasirox (Exjade)
  • Deferrioxamine (Desferal)
  • Deferiprone (Ferriprox)



Method of Administration

To take an Exjade dispersible tablet, patients have to completely disperse the tablets in water, orange juice or apple juice and drink. It should be administered at same time each day on an empty stomach, at least 30 minutes before food. To achieve optimal adherence, few barriers do exist:
  • Gastrointestinal tolerability
  • Palatability issues
  • A lengthy mixing process
  • Consumption on an empty stomach
  • Risk of patients failing to consume full dose
  • Using wrong/improper diluents
This eventually led to the development of a new film-coated tablet formulation of Exjade, which offers these benefits:
  • May be taken with or without a light (low-fat) meal (containing ~250 calories and <7% fat content)
  • No preparation or mixing required. For patients who are unable to swallow a whole tablet, it may be crushed and sprinkled on soft food.
  • Does not contain lactose and sodium lauryl sulfate.

NOTE: Despite the potential advantages offered, one could not deny that oral solution is often the preferred way to dose a young child.



Dispersible and Film Coated Tablet

In phase II ECLIPSE study, adverse events (overall), consistent with the known deferasirox safety profile, were reported in similar proportions of patients for each formulation (dispersible tablet and film coated tablet), with a lower frequency of severe events observed in patients receiving film coated tablet.

  • Laboratory parameters (serum creatinine, creatinine clearance, alanine aminotransferase, aspartate aminotransferase and urine protein/creatinine ratio) generally remained stable throughout the study.

It is very important to take note that the dose for Exjade film coated tablet is ~30% lower than Exjade dispersible tablet (doses rounded to the nearest whole tablet or sachet) due to higher bioavailability.To illustrate, if a patient is currently taking deferasirox dispersible tablet at 20 mg/kg/day, their dosage with deferasirox film coated tablet should be 14 mg/kg/day. Similarly, we can use the equations below to do dose conversion:

  • Exjade dispersible tablet 500 mg = Exjade film coated tablet 360 mg
  • Exjade dispersible tablet 125 mg = Exjade film coated tablet 90 mg



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