Safety and efficacy of iron sucrose in patients sensitive to iron dextran: North American clinical trial

doi:10.1053/ajkd.2000.8276

American Journal of Kidney Diseases

Volume 36, Issue 1, July 2000, Pages 88-97

https://doi.org/10.1053/ajkd.2000.8276 Get rights and content

Abstract

Sensitivity to iron dextran is a potent obstacle to maintaining optimum iron status in patients with dialysis-associated anemia. As part of the North American clinical trials for iron sucrose injection, we examined the effect of intravenous (IV) iron sucrose in 23 hemodialysis patients with documented sensitivity to iron dextran, ongoing epoetin alfa therapy, and below-target-range hemoglobin (Hgb) levels (<11.0 g/dL). We assigned patients to treatment groups according to whether reactions they had experienced to iron dextran were judged to be mild (n = 16; group A) or severe (n = 7; group B). We prospectively examined adverse events and vital signs after administering 100 mg of IV iron sucrose in each of 10 consecutive dialysis treatment sessions and compared results with those recorded in each of three consecutive dialysis sessions without iron treatment. We administered iron sucrose by IV push over 5 minutes to group A patients and by IV push over 5 minutes or IV infusion over 15 to 30 minutes to group B patients. We did not administer a test dose. Results showed no serious adverse drug reactions after a total of 223 doses of iron sucrose (184 doses by IV push, 39 doses by IV infusion). Intradialytic blood pressure changes after IV iron sucrose injection did not differ from those recorded during dialysis sessions without treatment. An increase in values for Hgb, hematocrit, transferrin saturation, and ferritin, coupled with no significant change in epoetin dose and a decrease in total iron-binding capacity, confirmed the efficacy of iron sucrose injection in managing anemia. We conclude that iron sucrose injection is safe and effective in the management of anemia in patients sensitive to iron dextran and can be administered without a test dose by IV push or infusion.

Section snippets

Iron sucrose injection

American Regent Laboratories, Inc (Shirley, NY) provided iron sucrose as Fe[III] hydroxide sucrose complex in water at an alkaline pH (Venofer; a registered trademark of Vifor International, Inc, St Gallen, Switzerland), 100 mg in 5-mL vials. The polynuclear inner sphere Fe[III] hydroxide is superficially surrounded by a large number of sucrose molecules, resulting in an overall complex molecular weight of approximately 43,000 d.⁹

Purpose

This was an open-label, single-arm, prospective study to assess

Results

Twenty-three patients were enrolled, and 22 patients completed treatment. One patient in group A withdrew after being administered five doses of iron sucrose when unstable angina unrelated to iron therapy developed after dialysis and required hospitalization for further evaluation. Two patients in group A missed one dose each. The remaining 13 patients in group A and all 7 patients in group B were administered 10 doses each. Results from the 23 patients, including 16 patients in group A and 7

Discussion

Our results, the first to examine the safety of iron sucrose administration in iron dextran sensitivity, clearly establish that patients sensitive to iron dextran can safely be administered iron sucrose by IV push or infusion without the need for a prior test dose. Among 23 patients with documented iron dextran sensitivity who were administered 184 doses of iron sucrose by IV push and 39 doses by IV infusion, only 2 patients showed adverse drug reactions, limited to two transient, self-limited

Acknowledgements

Acknowledgment: The following principal investigators participated in the study: C. Charytan, Flushing, NY; I. Cohen, San Diego, CA; N. Levin, New York, NY; J. Roman-La Torre, Dallas, TX; D. Van Wyck, Tucson, AZ; and S. Zeig, Ft Lauderdale, FL.

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Intravenous infusions of ferumoxytol compared to oral ferrous sulfate for the treatment of anemia in pregnancy: a randomized controlled trial
2023, American Journal of Obstetrics and Gynecology MFM
Iron-deficiency anemia in pregnancy is highly prevalent and presents significant risk to patients. Initial treatment is often with oral medication. We hypothesized that intravenous ferumoxytol would result in superior treatment of anemia as compared to oral ferrous sulfate.
This study aimed to investigate whether 2 infusions of intravenous ferumoxytol are superior to the use of twice-daily oral ferrous sulfate for the treatment of iron-deficiency anemia in pregnancy.
A randomized controlled trial was performed in which participants with anemic (hemoglobin <11 g/dL and hematocrit <33%) were allocated to receive either 2 infusions of 510 mg of intravenous ferumoxytol approximately 7 days apart, or 325 mg oral ferrous sulfate twice daily from enrollment to the end of their pregnancy. Participants were randomized in a 1:1 ratio to each treatment. Our primary outcome was the change in maternal hemoglobin. Secondary outcomes included maternal iron indices, maternal safety, and maternal tolerability.
There were 124 participants (N=62 per group). In the intravenous iron group, the mean change in hemoglobin was 1.86 g/dL (95% confidence interval, 1.57 g/dL–2.14 g/dL) and in the oral group was 0.79 g/dL (95% confidence interval, 0.42 g/dL–1.17 g/dL) (P<.0001). The median change in ferritin between groups was 64.5 (range, 31–364) vs 8 (range, −436 to +167) (P=.0001). The median change in iron between groups was also statistically significant with 47.5 ug/dL (range, −133 ug/dL to +664 ug/dL) in the intravenous group vs 8.5 ug/dL (range, −313 ug/dL to +437 ug/dL) in the oral iron group (P=.001).
Intravenous ferumoxytol was well tolerated, and it was associated with statistically significant increases in maternal hemoglobin, hematocrit, iron, and ferritin compared to oral ferrous sulfate.
Associations of Iron Sucrose and Intradialytic Blood Pressure
2023, American Journal of Kidney Diseases
Intradialytic hypotension and intradialytic hypertension are associated with morbidity and mortality in hemodialysis (HD). Many factors can contribute to intra-HD blood pressure (BP) changes, such as drugs with vasoactive properties that can destabilize an already tenuous BP. Intravenous iron sucrose is commonly administered to correct iron deficiency; however, its reported associations with altered hemodynamics have not been consistent.
Prospective cohort study.
950 outpatients receiving maintenance HD.
Iron sucrose administered during HD.
Intradialytic hypotension, intradialytic hypertension, systolic blood pressure parameters.
Unadjusted and adjusted Poisson and linear repeated measures regression models.
The mean age of patients included in the study was 53 ± 22 years, 43% were female, and 38% were Black. Mean pre-HD SBP was 152 ± 26 (SD) mm Hg. At baseline, the patients who received higher doses of iron sucrose tended to have diabetes, have longer HD sessions, and have a higher frequency of erythropoiesis-stimulating agent use, compared with those who did not receive iron sucrose. In adjusted models, higher doses of iron sucrose were associated with an 11% lower rate of intradialytic hypotension (incidence rate ratio [IRR] for iron sucrose ≥ 100 mg vs 0 mg, 0.89 [95% CI, 0.85-0.94]). In adjusted analyses, the administration of higher doses of iron sucrose during HD was associated with intradialytic hypertension (IRR for iron sucrose ≥ 100 mg vs 0 mg, 1.07 [95% CI, 1.04-1.10]).
Nonavailability of the precise iron sucrose formulation (volume), laboratory data for each HD session, and outpatient medications. Objective measures of volume status, home medications, and symptom data were not recorded in this study.
We observed an independent association of intravenous iron sucrose administration during HD with a lower risk of intradialytic hypotension and higher risk of intradialytic hypertension. Future studies to better understand the mechanisms underlying these associations are warranted.
Intradialytic hypotension and intradialytic hypertension are common among patients on hemodialysis, and they are associated with morbidity and mortality. Although many factors may contribute to these risks, medications administered during hemodialysis play an important role. We studied the significance of the intravenous iron sucrose used to treat iron deficiency and the impact it may have on blood pressure during dialysis. In our study of 950 outpatient hemodialysis patients, we observed that administration of iron sucrose was associated with higher systolic blood pressure (during and after hemodialysis sessions) as well as a lower risk of intradialytic hypotension. We also observed that higher doses of iron sucrose are associated with the development of intradialytic hypertension.
Practical Guidance for the Evaluation and Management of Drug Hypersensitivity: Specific Drugs
2020, Journal of Allergy and Clinical Immunology: In Practice
Citation Excerpt :
Switching agents can be considered in patients with mild to moderate reactions, but expert panels advise avoiding all parenteral iron after a severe reaction.916 Ferric gluconate and iron sucrose, but not ferumoxytol, are considered alternatives for patients sensitive to iron dextran.902,923,924 Desensitization to HMW iron dextrans has been reported.925,926
Synthesis and characterization of a new Inonotus obliquus polysaccharide-iron(III) complex
2015, International Journal of Biological Macromolecules
A new Inonotus obliquus polysaccharide-iron(III) complex (IOPS-iron) was synthesized and characterized. The preparation conditions of IOPS-iron(III) were optimized and the physicochemical properties were characterized by physicochemical methods, scanning electron microscopy (SEM), electron paramagnetic resonance (EPR) spectroscopy, fourier transform infrared (FTIR) spectroscopy, circular dichroism (CD) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy, respectively. The highest iron content of IOPS-iron(III) complex (19.40%) was obtained at the conditions: the ratio of IOPS and FeCl₃•6H₂O was 3:5 (w/w), the pH value of alkali solution was 10, the reaction temperature was 30 °C and the reaction time was 6 h. The iron(III) was shown to be bound through the binding sites of the polysaccharide IOPS and it could form spatially separated iron centers on the polysaccharide backbone. IOPS-iron(III) complex was found to have good digestive availability and antioxidant activities in the in vitro assays, which suggested the IOPS-iron(III) complex might be used as a new iron supplement candidate.
The safety of intravenous iron preparations: Systematic review and meta-analysis
2015, Mayo Clinic Proceedings
To amass all available evidence regarding the safety of intravenous (IV) iron preparations to provide a true balance of efficacy and safety.
Systematic review and meta-analysis of all randomized clinical trials comparing IV iron to another comparator. All electronic databases until January 1, 2014, were reviewed. Primary outcome was occurrence of severe adverse events (SAEs). Secondary outcomes included all-cause mortality and other adverse events (AEs). Subgroup analysis was performed on the basis of type of IV iron, comparator, treated condition, and system involved.
A total of 103 trials published between 1965 through 2013 were included. A total of 10,390 patients were treated with IV iron compared with 4044 patients treated with oral iron, 1329 with no iron, 3335 with placebo, and 155 with intramuscular iron. There was no increased risk of SAEs with IV iron (relative risk [RR], 1.04; 95% CI, 0.93-1.17; I²=9%). Subgroup analysis revealed a decreased rate of SAEs when IV iron was used to treat heart failure (RR, 0.45; 95% CI, 0.29-0.70; I²=0%). Severe infusion reactions were more common with IV iron (RR, 2.47; 95% CI, 1.43-4.28; I²=0%). There was no increased risk of infections with IV iron. Gastrointestinal AEs were reduced with IV iron.
Intravenous iron therapy is not associated with an increased risk of SAEs or infections. Infusion reactions are more pronounced with IV iron.
Comparison of the safety and efficacy of 3 iron sucrose iron maintenance regimens in children, adolescents, and young adults with CKD: A randomized controlled trial
2013, American Journal of Kidney Diseases
Citation Excerpt :
Twenty-nine nonserious drug-related events in 21 patients were seen, which gave a nonserious adverse drug event per-patient incidence of 4.4% and a per-exposure incidence of 0.34%. Two smaller studies of adults showed similar results.18,19 In the present study, slightly more than one-half of each treatment group experienced at least one treatment-emergent adverse event; however, only one such event prompted an early study exit and there were no differences in the incidence of adverse events when comparing the 3 dosage regimens.
Iron deficiency is a common cause of anemia in young persons with chronic kidney disease (CKD). Iron repletion with intravenous (IV) iron formulations has been studied in children; maintenance IV iron regimens have not been reported extensively.
A multicenter randomized trial of IV iron sucrose.
145 children, adolescents, and young adults with CKD receiving erythropoiesis-stimulating agent (ESA) therapy were stratified by dialysis category (hemodialysis, peritoneal dialysis, or non−dialysis dependent) and weight (<50 and ≥50 kg).
Patients were randomly assigned to 1 of 3 dosing arms: 0.5, 1.0, or 2.0 mg/kg (maximum single dose, 100 mg), stratified into hemodialysis versus nonhemodialysis (peritoneal dialysis or non−dialysis-dependent CKD) groups. Patients treated with hemodialysis received study medication once every other week for 6 doses. Patients in the nonhemodialysis group received study medication once every 4 weeks for 3 doses.
We assessed adverse event rates between dosing groups. The main clinical end point was a composite of hemoglobin level ≥10.5-14.0 g/dL, inclusive; transferrin saturation ≥20%-50%, inclusive; and stable ESA dosing (±25% of baseline dose).
Between-group difference for composite clinical end point rate attainment was −3.9% (95% CI, −21.4% to 13.7%) for the 1.0-mg/kg group versus 0.5-mg/kg group, +3.9% (95% CI, −15.1% to 23.0%) for the 2-mg/kg group versus 0.5-mg/kg group, and +7.8% (95% CI, −10.9% to 26.5%) for the 2-mg/kg group versus 1-mg/kg group. No differences were noted between regimens in reported adverse effects, which were all minor.
Absence of a control group receiving no IV iron. Short duration of intervention and observation. A small proportion of patients having achieved the primary clinical outcome.
IV iron sucrose at a dose of 0.5 mg/kg at the intervals prescribed is noninferior to higher doses in maintaining hemoglobin levels >10.5 g/dL in children, adolescents, and young adults receiving ESA therapy.

View all citing articles on Scopus

^*: Received November 3, 1999; accepted in revised form January 28, 2000.

^**: Supported in part by Luitpold Pharmaceuticals and American Regent Laboratories, Inc as part of their Investigational New Drug clinical US trials for Venofer.

^*: Address reprint requests to David B. Van Wyck, MD, Department of Medicine, PO Box 245099, Arizona Health Sciences Center, Tucson, AZ 85724. E-mail: [email protected]

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Original InvestigationSafety and efficacy of iron sucrose in patients sensitive to iron dextran: North American clinical trial*,**,*

Abstract

Section snippets

Iron sucrose injection

Purpose

Results

Discussion

Acknowledgements

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Lancet

Am J Kidney Dis

J Allergy Clin Immunol

Am J Kidney Dis

Intravenous iron dextran in clinical medicine

JAMA

Oversaturation of transferrin after intravenous ferric gluconate in haemodialysis patients

Nephrol Dial Transplant

Safety of intravenous injection of iron saccharate in haemodialysis patients

Nephrol Dial Transplant

European best practice guidelines for the management of anaemia in patients with chronic renal failure

Nephrol Dial Transplant

Structure/histotoxicity relationship of parenteral iron preparation

Arzneimittelforschung

Iron dextran in chronic renal failure

Semin Dial

Injectable medications for hemodialysis patients

Am J Nephrol

Comparative response to single or divided doses of parenteral iron for functional iron deficiency in hemodialysis patients receiving erythropoietin (EPO)

Clin Nephrol

Serum sickness from iron-dextran administration

Acta Haematol (Basel)

Allergic purpura following intravenous administration of iron dextran

Acta Haematol

Pulmonary edema: Atypical anaphylactoid reaction to intravenous iron dextran

Am J Nephrol

Experimental Immunochemistry

Original Investigation
Safety and efficacy of iron sucrose in patients sensitive to iron dextran: North American clinical trial*,**,*