Sodium ferric gluconate complex in hemodialysis patients: adverse reactions compared to placebo and iron dextran.
BACKGROUND
Parenteral iron is often required by hemodialysis patients to maintain adequate iron stores. Until recently, the only available form of intravenous iron was iron dextran, which is associated with significant adverse reactions, including anaphylaxis and death. Sodium ferric gluconate complex (SFGC) was recently approved for use in the U.S. under FDA's priority drug review. This Phase IV study was designed to evaluate the safety of a single dose of intravenous SFGC as compared to placebo and a historical iron dextran control.


METHODS
This multicenter, crossover, randomized, double blind, placebo-controlled prospective comparative study was performed in hemodialysis patients requiring at least 125 mg of elemental iron. The historical control was obtained from a meta-analysis of four publications examining outcomes in patients exposed to iron dextran. SFGC naïve patients were administered SFGC without a test dose, undiluted, at a rate of 125 mg over 10 minutes, and compared to placebo comprising bacteriostatic saline.


RESULTS
A total of 2534 patients were enrolled. The incidence of drug intolerance (an adverse event precluding re-exposure) was significantly less [0.44%, confidence interval (CI) 0.21 to 0.71%] after SFGC as compared to the iron dextran control (2.47%, CI 1.87 to 3.07%, P < 0.0001), but higher than after placebo (0.1%, P = 0.02). There was no difference found between SFGC and placebo in serious adverse events. A single life-threatening event occurred after SFGC (0.04%, CI 0.00 to 0.22%), which was significantly less than following iron dextran (0.61%, CI 0.36 to 0.86%), P = 0.0001.


CONCLUSIONS
SFGC is well tolerated when given by intravenous push without a test dose. SFGC has a significantly lower incidence of drug intolerance and life-threatening events as compared to previous studies using iron dextran. The routine use of iron dextran in hemodialysis patients should be discontinued.
Michael
Beckie
B
Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. Beckie.Michael@mail.tju.edu
Coyne
Daniel W
DW
Fishbane
Steven
S
Folkert
Vaughn
V
Lynn
Robert
R
Nissenson
Allen R
AR
Agarwal
Rajiv
R
Eschbach
Joseph W
JW
Fadem
Stephen Z
SZ
Trout
J Richard
JR
Strobos
Jur
J
Warnock
David G
DG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000707:Anaphylaxis / Q000139:chemically induced; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy* / Q000209:etiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007275:Injections, Intravenous; D007505:Iron-Dextran Complex / Q000008:administration & dosage / Q000009:adverse effects*; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011446:Prospective Studies; D006435:Renal Dialysis
D000806:Angiotensin-Converting Enzyme Inhibitors; D005290:Ferric Compounds; D010919:Placebos; D007505:Iron-Dextran Complex; C035552:ferric gluconate