Safety and Effectiveness of 100 mg/kg/day Deferiprone in Patients with Thalassemia Major: A Two-Year Study

Abstract

Deferiprone at a dose of 75 mg/kg/day is not sufficiently effective to maintain iron stores at a level which has been considered safe in all patients with iron overload. Our main aim was to determine the safety of long-term therapy with high-dose (100 mg/kg/day) deferiprone. A secondary aim was to determine the efficacy of this high dose. Twelve thalassemia major patients received deferiprone at a dose of100 mg/kg/day over 2 years. Transient aspartate aminotransferase increase (8 patients), gastrointestinal discomfort (3 patients) and arthralgia (2 patients) were the most commonly reported side effects. None of the patients discontinued therapy. The mean serum ferritin level fell from 3,901 ± 3,618 to 1,790 ± 2,205 µg/l after 2 years (p < 0.05). Five of the 12 patients continued to receive deferiprone for an additional 3 years. No new side effects were encountered. The mean serum ferritin level in this subgroup was initially 2,510 ± 332 µg/l and dropped to 1,511 ± 664 µg/l after 5 years (p < 0.05). Liver iron levels at the end of the 2-year study ranged from 1.0 to 30.9 mg/g dry weight, 3 of the patients having levels above 15 mg/g.

How I treat transfusional iron overload

“…The usual starting dose is 75 mg/kg per day but, provided it is well tolerated, doses up to 100 mg/kg per day can be given to enhance iron excretion. 34,35 Patient compliance is excellent compared with DFO. 33 DFP has the lowest molecular weight of the 3 chelators and penetrates cells to chelate iron from intracellular compartments, such as lysosomes and mitochondria.…”

Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions

“…Typical dosage for deferiprone is 75 mg/kg/d in 3 divided doses, up to 100 mg/kg daily. 3,10 Deferasirox Deferasirox (ICL670, Exjade) belongs to a new class of oral tridentate chelator, N-substituted bis-hydroxyphenyltriazoles. Deferasirox, the result of a concerted discovery program, underwent extensive safety testing and clinical trials including preclinical studies, 11 initial phase 1 and iron balance studies, 12 phase 2 efficacy studies in adult 13 and pediatric 14 thalassemia patients, patients with a variety of anemias or unable/noncompliant with DFO, 15 and the phase 3 clinical trial discussed here.…”

Thyroid dysfunction in thalassaemic patients: ferritin as a prognostic marker and combined iron chelators as an ideal therapy

“…The majority of the DFP iron complex is excreted in the urine and the remainder in the feces. The most serious side effect associated with its use is agranulocytosis, which occurs in 2% of patients (13).…”