Deferiprone, also known as L1, is an orally active
iron chelator that has been studied extensively in clinical trials. The sporadic occurrence of
agranulocytosis in association with
deferiprone and the highly variable frequency of other possible side effects such as
arthralgia have created uncertainty about the true incidence of
deferiprone-related complications. A multi-center, 1-year trial was initiated to determine the safety profile of
deferiprone. Using the Apotex formulation of
deferiprone, 187 patients with
thalassemia who were unable or unwilling to use
deferoxamine were enrolled in four centers; 162 patients completed one year of
therapy.
Agranulocytosis (ANC < 500/mm3) occurred in one patient after 15 weeks of treatment, was not accompanied by
infection and resolved following treatment with
G-CSF. Nine other subjects developed less severe
neutropenia (ANC 500-1500/mm3) with the lowest absolute neutrophil count reaching 500-1250/mm3. The
neutropenia in these patients developed after 1-50 weeks of
therapy, frequently accompanied febrile illnesses, and occurred predominantly in non-splenectomized patients. Reasons other than
neutropenia for discontinuing use of
deferiprone included
nausea (4), voluntary withdrawal (3), high ALT (2), platelet count < 100,000/mm3 (2), low but unconfirmed
ANC (1), protocol violation (1)
fatigue (1), and depression (1). Mean ALT levels rose within three months of
therapy and stabilized thereafter.
Arthralgia and
nausea and/or
vomiting occurred in 6% and 24% of subjects, respectively. In this multi-center trial with weekly monitoring of blood counts, the incidence of
agranulocytosis was 0.58 per 100 patient-years, and the frequency of
agranulocytosis after one year was 0.5%. These findings support the safety of this formulation of
deferiprone, using the careful monitoring system employed in this trial.