Safety and effectiveness of extended versus shortened iron dextran infusion time for the treatment of iron deficiency anemia
Authors: Sarah Deitering, Lisa Anselmo, Allison Burnett, Bernadette Jakeman
Journal: American Journal of Hematology (2016)

To the Editor: Iron deficiency anemia is one of the most common nutritional disorders in the world, affecting approximately 25% of the world's population 1. First-line management in the majority of cases is oral iron, although frequency of dosing, gastrointestinal adverse events (AEs), and absorption issues often lead to treatment with parenteral iron. While several parenteral iron formulations are available, iron dextran has the benefit of being a one-time, total dose infusion. Historically, iron dextran was administrated with premedication and over several hours out of concern for serious AEs. Notably, serious AEs are much less common (<1:200,000) with the low molecular weight (LMW) formulations than the high molecular weight (HMW) ones 2. In 2011, Auerbach et al. published the results of a retrospective study of 396 patients which found that shortened infusion iron dextran with limited steroid premedication was both safe and effective 3. The authors also found an increased AE risk associated with >2 drug allergies. In response to this study, our institution implemented a protocol for the infusion of 1 g of LMW iron dextran over 1 hr. An additional 30-min infusion time was used for each 500 mg beyond the traditional 1 gram dose and premedication use was only recommended with >2 drug allergies. We conducted a retrospective cohort study of adults receiving iron dextran for the first time at a cancer center located on the campus of a regional academic medical center. Patients were divided into shortened infusion (rate ≥12 mg/min) and extended infusion (rate <12 mg/min) iron dextran groups. Infusion time was based on rounding up to the nearest 500 mg dose. A total of 241 were screened for inclusion, 34 of whom were excluded (20 previously received iron dextran, 6 concurrent chemotherapy, 4 incomplete time information, 3 experienced an AE during test dose, and 1 did not receive iron dextran). Of those who met inclusion, 92 (45%) received the extended infusion and 115 (55%) received the shortened infusion. At baseline, there were no statistically significant differences between groups with the exception of more females (81.5% vs. 67.8%; P = 0.026) and premedication use (81.5% vs. 46.9%; P < 0.001) in the extended infusion group. The most common indications for parenteral iron were gastrointestinal or uterine bleeding (35%) and cancer (28%). AEs and AEs requiring medication intervention were not significantly different between groups (Table 1). The most common AEs were abdominal pain and nausea. Throat itching occurred in two (both in the extended infusion group) and led to infusion discontinuation in one. The univariate analysis of baseline characteristics to identify correlation with AEs only detected a significant association with celiac disease. Celiac disease, as well as those variables that differed significantly at baseline between the two groups (female sex and premedication use), were incorporated into the multiple logistic regression. In that analysis, celiac disease remained the only characteristic significantly associated with increased risk of developing an AE (OR 39.9, 95% CI 3.8–417.4; P = 0.002). Of the four with celiac disease in the study, three developed an AE. There were also no significant differences between groups with regard to average increase in hemoglobin or any of the iron indices (Table 1). Chair time was significantly less, by an average of 1.7 hr, in the shortened infusion group (Table 1). The results of this study show that there is no difference in AEs and effectiveness between shortened and extended infusion iron dextran. AEs were relatively uncommon and nonlife threatening. After controlling for gender and premedication use, celiac disease was the only baseline characteristic significantly associated with an increased likelihood of an AE. Although previous studies have not reported a relationship between celiac disease and AEs, it may be related to the immune-mediated nature of the disease. However, this association should be viewed cautiously as there were only four (1.9%) with celiac disease. Notably, premedication use did not significantly reduce the risk of developing an AE. While premedication use did decline significantly after protocol implementation, it is suspected that many continued to receive premedication because of provider comfort. Anti-histamines were the most commonly administered premedication, despite the lack of evidence and their ability to cause AEs themselves 4. While it is difficult to differentiate, it is possible that many of the AEs experienced were secondary to anti-histamine use rather than iron dextran. Those with >2 drug allergies made up a relatively large percentage of the population (12%) but, unlike the previous study, we found no significant association between multiple drug allergies and AEs. This could be explained by premedication use in this group, although this is common practice in many studies and the protective effect of premedication is not convincing 3, 5. Finally, the switch to shortened infusion iron dextran also has the advantage of significantly less chair time. This time savings is beneficial as it allows more to receive treatment and requires less time spent in clinic. Additionally, it improves reimbursement rates, as a clinic is often paid more for the first hour of infusion than subsequent hours. Although several studies have assessed the safety and effectiveness of shortened infusion iron dextran, this study is unique in that it directly compares extended versus shortened infusion in a general population 3, 5, 6. Limitations include the retrospective nature and infrequency of severe AEs. Since severe AEs are exceedingly rare, especially with the disappearance of HMW formulations, it is logistically challenging to collect a sample size that would have a high likelihood of capturing such events. Future studies are necessary to further elucidate risk factors associated with developing an AE in order to identify if certain populations may benefit from premedication. In summary, iron dextran is a convenient parenteral treatment option that allows for total iron deficit repletion, which is particularly beneficial for those who live in rural areas or have difficulty getting into clinic. Although historical concerns regarding serious iron dextran AEs have led to standard extended infusion times, the results of this study support the transition to shortened infusion as safe, effective, and associated with significant chair time savings. Sarah Deitering,1* Lisa Anselmo,2 Allison Burnett,1 and Bernadette Jakeman3 1Department of Pharmacy, University of New Mexico Hospital, Albuquerque, New Mexico; 2Department of Pharmacy, University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico; 3Department of Pharmacy Practice and Administrative Sciences, University of New Mexico College of Pharmacy, Albuquerque, New Mexico