Once-daily tablet treats iron overload

December 12, 2005

The Food & Drug Administration has approved deferasirox (Exjade, Novartis Pharmaceuticals) for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in adults and children age two and older. "Iron overload is a potentially fatal consequence among patients with sickle cell disease, myelodysplastic syndromes, and thalassemia who regularly receive blood transfusions," said Alice Cohen, M.D., director of the division of hematology and oncology at Newark Beth Israel Medical Center, Newark, N.J. If left untreated, excess iron may lead to significant damage to the heart, liver, and other vital organs.

The body has no inherent mechanism for removing excess iron; therefore, patients must take chelation therapy for transfusion-related iron overload. "Currently, many patients receive treatment with deferoxamine [Desferal, Novartis], a subcutaneous infusion lasting eight to 12 hours," said Cohen. "Patients are usually treated with Desferal for five to seven nights per week for as long as they continue to require treatment," she added.

In contrast, new deferasirox is a once-daily oral tablet designed to dissolve rapidly in water, apple juice, or orange juice. Approval of deferasirox, Cohen anticipates, will enhance patient acceptance and adherence, and may be a welcome alternative to the cumbersome standard therapy. "The availability of an oral iron chelator may help improve the quality of life for many patients," she said.

The manufacturer suggests that serum creatinine should be assessed before treatment initiation, and monitored monthly thereafter. Moreover, auditory and ocular disturbances have been reported with deferasirox treatment, and monitoring is advised.

According to its maker, deferasirox should be initiated at 20 mg/kg body weight when a patient has evidence of chronic iron overload, such as the transfusion of approximately 100 mL/kg of packed red blood cells (about 20 units for a 40-kg patient) and a serum ferritin level consistently greater than 1000 mcg/L.

Monthly serum ferritin measurements should be used to adjust the dose over time, taking into account the patient's response and therapeutic goals. If the serum ferritin falls consistently below 500 mcg/L, the prescriber should consider temporarily interrupting deferasirox therapy. Novartis urges that doses of deferasirox should not exceed 30 mg/kg/day, due to limited experience with doses above this level.

Although deferasirox has a lower affinity for aluminum than iron, the package labeling states that deferasirox should not be taken with aluminum-containing antacid preparations. Additionally, deferasirox should not be combined with other iron chelator therapies, since the safety of such combinations has not been established. Deferasirox may be commercially available this month.

The Author is a writer and hospital pharmacist based in New Jersey.