Twice Daily Use of Deferasirox Is More Effective in Decreasing Serum Ferritin
Authors: Gumruk Fatma , Unal Sule , Bayhan Turan , Hazirolan Tuncay , Tuncer A. Murat , Cetin Mualla 
Published: November 2019

Abstract
Patients with beta-thalassemia major (BTM) are prone to tissue iron overloading in case that not adequately chelated. Among the iron chelators, development of oral chelators have improved patients’adherence to treatment. Deferasirox is a tridentate iron chelator, used once daily with a half life of 8-16 hours. The negative chelation effect is achieved at doses above 30 mg/kg/day and the currently FDA-approved maximum dose for use in patients is 40 mg/kg/day. However, some of the deferasirox side effects are dose-dependent increasing the occurences of adverse events at high doses. Additionally, although there is data that non-transferrin bound iron is effectively decreased by once daily dosing, the iron chelation effects of the drug may increase since in some of the patients half-life of the drug has been reported to be even less than 7 hours. Herein, we compared the iron chelation effect and tolerability of deferasirox in the same patients who were using deferasirox at a dose of 40 mg/kg/day.
The patients with BTM who were under iron chelation with deferasirox at a dose of median 40 mg/kg/day (38-41) once daily for at least 6 months were included (n=10). These patients were receiving deferasirox at a maximum dose in the enrollment to the study related to either serum ferritin levels above 1500 ng/ml or moderate to severe iron loading in cardiac or liver tissues. These patients were put on a twice daily regimen of the same dose and followed up at a median time period of 7 months (4-17). The serum ferritin, ALT, creatinine levels and T2* MRI of heart and liver were obtained at the beginning of the twice daily dosing and by the end of the follow-up time. Patients were given a questionairre to investigate the tolerability and satisfaction of once daily and twice daily use.
The median age of the study group was 21 years (3-34), hal were males. The patients’ serum ferritin, cardiac and hepatic iron loading levels were summarized in Table 1. There was a statistically significant decrease in serum ferritin levels with twice daily use of deferasirox compared to once daily use of the same dose. The initial and follow-up ALT and serum creatinine levels did not differ significantly (p>0.05). None of the patient required a dose reduction or cessation of the drug related to a toxicity. The major tolerability concern of the patients in once daily dosing was nausea in 2 of the patients (20%). After twice daily dosing the major concern of the patients was twice daily use of the drug itself in 2 patients (20%). None of the patients reported nausea in twice-dosing. The patients’ satisfaction survey in the end of the study for once or twice daily use was for once daily use revealed preference for twice-use in 5 (50%) of the patients for either no nausea (n=2) with twice-use or better decrease in serum ferritin levels (n=3). Three (30%) preferred once daily use as a better way, related to lesser drug use. Two patients reported that there were no difference in terms of satisfaction.
In conclusion, twice daily use of deferasirox at higher doses is much better tolerated and causes a better decline in serum ferritin levels of already high iron burden. Further studies in larger sample groups may be more definitive.
Table 1. The initial and follow-up iron overloading evaluations Mean ± SD (Range) p Initial SF (ng/ml) Follow-up SF 2020±983 (1016-4128) 1533±1026 (521-4003) 0.047 Initial cardiac T2* MRI (ms) Follow-up cardiac T2* MRI 25.4±8.6 (14.6-38) 21.5±7.8 (13.8-30) 0.068 Initial liver T2* MRI (ms) Follow-up liver T2* MRI 3.6±1.9 (1.3-8) 6.7±5.1 (2.1-13.6) 0.465
SF: serum ferritin; SD: standard deviation

Disclosures
No relevant conflicts of interest to declare.