Chronic use of sodium ferric gluconate complex in hemodialysis patients: safety of higher-dose (> or =250 mg) administration.

BACKGROUND: Almost all hemodialysis (HD) patients require intravenous iron therapy to correct their anemia and maintain their iron stores. Sodium ferric gluconate complex (SFGC) is approved by the Food and Drug Administration (FDA) for treatment of iron deficiency anemia in HD patients at individual doses up to 125 mg over 10 minutes (12.5 mg/min) and has been shown to have a superior safety profile compared with iron-dextran. Higher individual doses of SFGC would permit more rapid repletion of iron stores and greater flexibility in maintenance iron therapy as well as simplify treatment of peritoneal dialysis patients and chronic kidney disease patients. METHODS: The authors reviewed the safety and tolerability of higher-dose SFGC infusions (> or =250 mg) in 144 HD patients who were previously tolerant to a single 125-mg dose of SFGC. These 144 patients received a total of 590 doses of > or =250 mg of SFGC; 571 doses were 250 mg SFGC, and most of these were infused over 1 hour, an infusion rate of 4.17 mg/min. The other 19 doses were 312.5 mg (n = 1), 375 mg (n = 14), and 500 mg (n = 4). Infusion rates varied from 1.22 mg/min to 25.0 mg/min. RESULTS: Only one patient was considered intolerant to higher-dosing SFGC after having pruritus after a second 250-mg dose of SFGC. Three patients had nonserious events that did not preclude further dosing of SFGC. CONCLUSION: Administration of 250 mg SFGC over 1 hour is safe and well tolerated. Individual doses of 375 mg and 500 mg SFGC also were well tolerated, but further research and experience are needed to confirm the safety and tolerance of these doses.

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.