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 µg/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 µg/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 µg/l, iron 68 ± 21 µg/dl, and iron saturation 30 ± 7.8%. At the end of study, mean ferritin was 609 ± 340 µg/l (p = 0.02), iron 75 ± 27 µg/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.


CONCLUSIONS
Ferric citrate was well tolerated by patients after 4 weeks with no significant clinical or biochemical adverse events related to exposure.
Circle Medical Management, Chicago, IL 60607, USA. mvsinsakul@gmail.com
Marvin
M
Sinsakul
Mohammed
M
Sika
Mark
M
Koury
Warren
W
Shapiro
Tom
T
Greene
Jamie
J
Dwyer
Mark
M
Smith
Stephen
S
Korbet
Julia
J
Lewis
D000328:Adult; D002614:Chelating Agents / Q000009:adverse effects*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000209:etiology / Q000517:prevention & control; D003116:Color; D003248:Constipation / Q000139:chemically induced; D005243:Feces; D005260:Female; D005290:Ferric Compounds / Q000009:adverse effects*; D005293:Ferritins / Q000097:blood; D006801:Humans; D007501:Iron / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010758:Phosphorus / Q000097:blood*; D006435:Renal Dialysis; D011795:Surveys and Questionnaires
D002614:Chelating Agents; D005290:Ferric Compounds; D010758:Phosphorus; C025314:ferric citrate; D005293:Ferritins; D007501:Iron