An alternative to continuous subcutaneous infusion of desferrioxamine in thalassaemic patients

Abstract

Summary. Sixteen patients with thalassaemia major were treated with subcutaneous desferrioxamine (DF) 50 mg/kg/d, 5 consecutive days a week, for 8 weeks. Every other week the total dose was administered by 12 h infusion pump or by rapid injection of the same dose (25 × 2 mg/kg) twice a day. The two methods of DF administration produced no significant differences in urinary iron excretion. No significant changes in serum ferritin levels were observed at the end of the study. Compared with continuous infusion, rapid injection is equally efficacious, does not induce serious side-effects, is better accepted by the patients, and can improve their compliance to the iron-chelating therapy.Keywords: iron overload, desferrioxamine, rapid infusion.Patients with thalassaemia major are at high risk of transfusional iron overload and require continuous chelating treatment to avoid severe complications such as cardiac failure. Administration of subcutaneous desferrioxamine (DF) by 12 h infusion pump is recommended for its efficacy and because it can be carried out at home (Britthenham et al, 1994). Compliance of thalassaemic patients, particularly adolescents, to this treatment is often poor, because the discomfort associated with using the pump greatly affects their quality of life (Cohen, 1987). In order to improve adherence to chelating therapy, we investigated the effects of rapid subcutaneous injection of DF as an alternative to conventional administration by infusion pump. MATERIAL AND METHODSThe study was carried out in 16 patients with thalassaemia major aged between 13 and 30 years (mean 21 . 2 years). All of them received regular blood transfusions every 2-3 weeks to maintain Hb levels above 9 . 5-10 g/dl, and 40-50 mg/kg/d subcutaneous DF by 12 h infusion pump, 5-6 d a week. After informed consent, all patients were given subcutaneous DF 50 mg/kg/d, 5 consecutive days a week, for 8 weeks, according to the following schedule: (1) 1 week during which the total dose of 50 mg/kg diluted in 20 ml distilled water was slowly administered by pump (12 h); (2) 1 week during which a dose of 25 mg/kg/d diluted in 10 ml water was rapidly injected twice a day, every 12 h. Urinary iron after DF was measured in all patients 2, 4, 6, 9, 11 and 13 d after each blood transfusion. At the end of the study, eight patients decided to continue the rapid injection treatment for another 8 weeks. Serum ferritin levels were measured by immunoradioassay at the start and at the end of the study in all patients. Statistical analysis was performed using t-test for paired data. RESULTSThere were no significant differences in urinary iron excretion after subcutaneous DF administered either in the traditional manner of 50 mg/kg/d by 12 h infusion or by rapid injection of the same overall dose twice daily (Table I).

Iron overload in patients with myelodysplastic syndromes

“…When evaluating the immediate efficacy of both regimens of DFO administration by measurements of UIE, we found no significant difference. Our observations were confirmed later in 16 patients with -thalassemia major by Di Gregorio et al [46]. It was also reported that all patients preferred the bolus administration, and no serious side effects were observed.…”

Development of a sensitive HPLC method to measure in vitro permeability of E- and Z-isomeric forms of thiosemicarbazones in Caco-2 monolayers

“…Though clinically effective, DFO has the drawback of having relatively high hydrophilicity, which reduces its ability to cross the lipid bilayer of cell membranes [17] and lowers its potential for absorption from the gastrointestinal tract. Consequently, the drug must be given parenterally, as a continuous subcutaneous infusion, or as a continuous intravenous infusion over long periods of time (12–24 h/day; 5–6 days/week) [18, 19]. On the other hand, ICL670 is absorbed more effectively by the intestine and also has a longer half-life than DFO [20].…”

Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload: an update

“…Subsequently, other studies confirmed these findings in thalassemic and nonthalassemic iron-overloaded patients. [5][6][7][8] More recently, we documented the long-term safety and efficacy of this method in 26 iron-overloaded adult patients. 9 Since then, we have received many letters from colleagues who wanted to start such a method of administration or who asked us for an update of our patients.…”