The Safety and Tolerability of Ferric Citrate as a Phosphate Binder in Dialysis Patients

Background: A phase II open-label study was conducted in hemodialysis patients evaluating the short-term safety, tolerability, and iron absorption with ferric citrate when used as a phosphate binder. Methods: Enrollment occurred in two periods. Period 1 recruited patients taking 6-15 pills/day of binder with phosphorus of >= 2.5 mg/dl. Period 2 recruited patients taking >= 12 pills/day of binder with phosphorus of >= 3.5 mg/dl. Participants with ferritin >= 1,000 mu g/l or transferrin iron saturation (TSAT) >= 50% at screening were excluded. Subjects discontinued their previous binders and started 4.5 g/day of ferric citrate (period 1) or 6 g/day (period 2) and were titrated for 4 weeks to maintain a phosphorus of 3.5-5.5 mg/dl. Chemistries and complete blood count were obtained weekly and a gastrointestinal questionnaire was administered at drug initiation and final visit. Iron therapy was permitted if the ferritin was < 500 mu g/l and TSAT < 30%. Results: Fifty-five subjects were enrolled. Four serious adverse events were reported; none were related to the study drug. Findings from the gastrointestinal questionnaire included stool discoloration (69%), constipation (15%), and bloating (7%). Mean iron parameters at the beginning of the study were ferritin 554 +/- 296 mu g/l, iron 68 +/- 21 mu g/dl, and iron saturation 30 +/- 7.8%. At the end of study, mean ferritin was 609 +/- 340 mu g/l (p = 0.02), iron 75 +/- 27 mu g/dl (p = 0.04), and TSAT was 35 +/- 13% (p = 0.001). Mean phosphorus and calcium levels were unchanged from baseline at the end of study. Conclusion: Ferric citrate was well tolerated by patients after 4 weeks with no significant clinical or biochemical adverse events related to exposure. Copyright (c) 2012 S. Karger AG, Basel