A safety, pharmacokinetic and pharmacodynamic investigation of deferasirox (Exjade, ICL670) in patients with transfusion-dependent anemias and iron-overload: a Phase I study in Japan.
ABSTRACT The pharmacokinetics (PK) and pharmacodynamics (PD) of the once-daily, oral ironchelating agent, deferasirox (Exjade, ICL670), have been evaluated further in a Phase I, openlabel, multicenter, dose-escalation study in Japanese patients with myelodysplastic syndromes, aplastic anemia, and other anemias. Deferasirox was initially administered as a single dose of 5 (n = 6), 10 (n = 7), 20 (n = 6) or 30 (n = 7) mg/(kg day) and then after 7 days seven daily doses were administered. Linear PK (C (max) and AUC) were observed at all doses after a single dose and at steady state, and dose-dependent iron excretion was observed. Pharmacokinetic/pharmacodynamic parameters were similar to those reported in a Caucasian beta-thalassemia cohort. Following the single- and multiple-dose phases, 21 of 26 patients progressed to a 3-year extension phase of the study, where dose reductions and increases [5-30 mg/(kg day)] were allowed following safety and efficacy assessments. In the interim, 1-year data show that deferasirox was well tolerated, with generally infrequent and mild adverse events. Reductions in serum ferritin levels were observed and a negative iron balance achieved at doses of 20-30 mg/(kg day). These data suggest that deferasirox has a stable and predictable PK/PD profile, irrespective of underlying disease or race, and a predictable and manageable safety profile suitable for chronic administration.
- Blood Cells Molecules and Diseases 04/2013; · 2.26 Impact Factor
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ABSTRACT: BACKGROUND: Deferasirox (DFX) is a novel iron chelator that has been shown to have similar efficacy and safety compared with deferoxamine (DFO) in patients with β-thalassemia. The aim of this study was to determine the cost utility of DFX versus DFO in β-thalassemia major patients from Iran's society perspective. STUDY DESIGN AND METHODS: A Markov model has been developed to determine lifetime cost and quality-adjusted life-years (QALYs) of patients. To estimate the annual cost of each method, a cross-sectional study was conducted among two groups of patients who received DFO and DFX (n = 100 and n = 45, respectively). Also a time trade-off method was used to estimate the utility of two strategies. Finally a one-way and probabilistic sensitivity analysis was conducted to examine the strength of the results. RESULTS: Our base-case analysis showed that estimated total lifetime costs per patient for DFX and DFO were 47,029 international dollar ($Int) and $Int143,522, respectively, while the estimated total discounted QALYs per person were 12.28 and 7.76, respectively. Calculated incremental cost-effectiveness ratio showed that DSX is a dominant therapy and its estimated lifetime net monetary benefit was $Int273,528. CONCLUSION: We conclude that the use of DFX instead of DFO represents a cost-effective use of resources for treatment of iron overload in patients with β-thalassemia from Iran's society perspective.Transfusion 12/2012; · 3.53 Impact Factor
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ABSTRACT: A 64-year-old woman developed pure red cell aplasia (PRCA) 4 years after thymectomy for thymoma. During anti-thymocyte globulin treatment, the patient developed cytomegalovirus pneumonia and was thus unable to continue immunosuppressive therapy and became transfusion dependent. Deferasirox was started for treatment with iron overload when serum ferritin increased to >1000 ng/mL. Seven months after initiation of deferasirox treatment, serum ferritin level decreased the normal range and the patient has remained transfusion independent thereafter. Deferasirox was discontinued when serum ferritin level decreased below 500 ng/mL, and she has maintained in complete remission over the last 15 months. Hypotheses have been raised regarding the improvement of hematopoiesis by deferasirox treatment, but the mechanism whereby this might be achieved remains unclear. Deferasirox treatment may be clinically beneficial both by reducing iron overload and by improving hematopoiesis in patients with PRCA.International journal of hematology 10/2013; · 1.17 Impact Factor