Combined therapy with deferiprone and desferrioxamine.
In a proportion of transfusion-dependent patients iron chelation with daily doses of deferiprone of 75 mg/kg body weight (b.w.) is inadequate. The effects on iron status of increasing the daily oral dose of deferiprone and/or combining deferiprone therapy with subcutaneous infusions of desferrioxamine have been studied in 13 transfusion-dependent patients. Raising the daily dose of deferiprone in nine patients from 75 mg/kg to 83-100 mg/kg resulted in a fall in serum ferritin in all nine patients (t test for paired samples, P = 0.0022). Combined therapy of daily deferiprone with subcutaneous desferrioxamine on 2-6 d each week in five patients (with an increased dose of deferiprone in three patients) resulted in a fall in serum ferritin in all five patients studied after 7-15 months (P=0.0791). No toxic side-effects attributable to either drug occurred in these five patients or in the nine patients in whom the dose of deferiprone was increased. The effects of the drugs given on the same day on urine iron excretion were additive. These results suggest that increasing the dose of deferiprone or combining subcutaneous desferrioxamine with deferiprone therapy are two methods by which efficacy of iron chelation with deferiprone can be improved in patients inadequately chelated by a daily dose of deferiprone of 75 mg/kg b.w. More extensive trials including full metabolic balance studies are needed to establish the safety and efficacy of long-term combined therapy.
Wonke
B
B
Department of Haematology, Whittington Hospital, London.
Wright
C
C
Hoffbrand
A V
AV
D000293:Adolescent; D000328:Adult; D000368:Aged; D000077543:Deferiprone; D003676:Deferoxamine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007501:Iron / Q000652:urine; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011728:Pyridones / Q000627:therapeutic use*; D013789:Thalassemia / Q000628:therapy*; D065227:Transfusion Reaction; D017086:beta-Thalassemia / Q000628:therapy
D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine