Sodium ferric gluconate complex in hemodialysis patients. II. Adverse reactions in iron dextran-sensitive and dextran-tolerant patients.
BACKGROUND
Iron dextran administration is associated with a high incidence of adverse reactions including anaphylaxis and death. Although dextran, rather than iron, is believed to be the cause of these reactions, it is not known whether iron dextran-sensitive patients can be safely administered another form of parenteral iron, sodium ferric gluconate in sucrose (SFGC).


METHODS
In a 69 center, prospective, double-blind, controlled trial of safety and tolerability of SFGC, the rate of reactions to SFGC and placebo in 144 iron dextran-sensitive patients was compared with 2194 patients who were previously tolerant to iron dextran preparations. Serum tryptase levels, a marker of mast cell degranulation, also were measured.


RESULTS
Among 143 iron dextran-sensitive patients exposed to SFGC, three (2.1%) were intolerant. All three had suspected allergic events to SFGC, including one patient with a serious reaction (0.7%). One dextran-sensitive patient (0.7%) had a suspected allergic reaction after placebo. In contrast, among 2194 iron dextran-tolerant patients, reactions to SFGC were significantly less common, with SFGC intolerance seen in seven patients (0.3%; P = 0.020), including five (0.2%) who had suspected allergic events (P = 0.010), but none who had serious events (0.0%; P = 0.061). Two iron dextran-tolerant patients (0.09%) had allergic-like reactions following placebo injections. Two of the three suspected allergic events in the iron dextran-sensitive group were confirmed as mast cell dependent by a 100% increase in serum tryptase, while there were no confirmed allergic events in the iron dextran-tolerant group. Long-term exposure to SFGC in iron dextran-sensitive patients resulted in intolerance in only one additional patient and no serious adverse events.


CONCLUSIONS
Patients with a history of iron dextran sensitivity had approximately sevenfold higher rates of reaction to both placebo and SFGC compared to iron dextran tolerant patients. However, logistic regression analysis, performed to account for the higher reaction rate to placebo, suggests that this increased reactivity was not drug-specific nor immunologically mediated, but represented host idiosyncrasy. These results support the conclusions that reactions to SFGC can be attributed to pseudoallergy, and that SFGC is not a true allergen.
Coyne
Daniel W
DW
Washington University School of Medicine, St. Louis, Missouri 63110, USA. Dcoyne@im.wustl.edu
Adkinson
N Franklin
NF
Nissenson
Allen R
AR
Fishbane
Steven
S
Agarwal
Rajiv
R
Eschbach
Joseph W
JW
Michael
Beckie
B
Folkert
Vaughn
V
Batlle
Daniel
D
Trout
J Richard
JR
Dahl
Naomi
N
Myirski
Pamela
P
Strobos
Jur
J
Warnock
David G
DG
D004342:Drug Hypersensitivity / Q000276:immunology; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D007505:Iron-Dextran Complex / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000276:immunology; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis; D012697:Serine Endopeptidases / Q000097:blood; D013395:Sucrose; D053802:Tryptases
D005290:Ferric Compounds; D013395:Sucrose; D007505:Iron-Dextran Complex; D012697:Serine Endopeptidases; D053802:Tryptases; C035552:ferric gluconate