Beta Thalassemia Medication

Medical therapy for beta thalassemia primarily involves iron chelation. Deferoxamine is an intravenously administered chelation agent currently approved for use in the United States. An oral chelation agent, deferiprone, has been approved for use in Europe and recently received approval in the United States (October, 2011) for the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate. Another orally administered chelation agent, deferasirox, was approved for use in the United States by the US Food and Drug Administration (FDA) in 2005. Guidelines on chelation treatment in thalassemia major have been published.^{[4, 5]}

However, another orally administered chelation agent, deferasirox, was approved for use in the United States by the Food and Drug Administration (FDA) in 2005.

Because fetal globin gene expression is associated with a milder phenotype, approaches to enhance intracellular Hb F levels (through drugs that activate gamma-globin gene expression) are under investigation. The 2 most widely studied drugs in this area are butyrates and hydroxyurea.^[6] More recently, new therapeutic targets have been reported, such as BCL11A.^[7]

Gene therapy for beta thalassemia is being pursued by several research groups. Obstacles to gene therapy include an inability to express high levels of the beta-globin gene in erythroid cells and an inability to transduce hematopoietic pluripotent stem cells at high efficiency. In one study, an adult patient with severe, transfusion-dependent beta thalassemia became transfusion independent for 21 months, 33 months after lentiviral beta-globin gene transfer, with peripheral blood hemoglobin being maintained at 9-10 g/dL.^[8]

Class Summary

These agents bind iron and promote excretion.

Deferoxamine (Desferal)

Deferoxamine is usually administered as a slow, subcutaneous infusion through a portable pump. It is freely soluble in water. Approximately 8 mg of iron is bound by 100 mg of deferoxamine. This agent is excreted in bile and urine, resulting in red discoloration. It readily chelates iron from ferritin and hemosiderin, but not from transferrin. Deferoxamine is most effective when it is administered as a continuous infusion.

Deferasirox (Exjade)

Deferasirox comes in tablet form for oral suspension. It is an oral iron chelation agent that has been demonstrated to reduce liver iron concentration in adults and children who receive repeated red blood cell (RBC) transfusions. It binds to iron with a high affinity, in a 2:1 ratio. Deferasirox has been approved to treat chronic iron overload due to multiple blood transfusions.

Treatment initiation is recommended with evidence of chronic iron overload (ie, transfusion of about 100 mL/kg packed RBCs, about 20 U for a 40-kg person, and serum ferritin level consistently >1000 mcg/L). Serum ferritin should be monitored every month, and dosage should be adjusted every 3-6 months based on ferritin measurements in increments of 5 or 10 mg/kg. If ferritin consistently falls below 500 mcg/L, consider holding the drug. The dose should not exceed 30 mg/kg/day.

Deferiprone (Ferriprox)

Deferiprone is an iron chelator indicated for patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate. Approval is based on a reduction in serum ferritin levels. No controlled trials have demonstrated a direct treatment benefit, such as improvement in disease-related symptoms, functioning, or increased survival. It is available as 500-mg, film-coated tablets.