Premedication with IV steroids effectively prevented anaphylactic reactions following ferumoxytol given as IV push in hematology and oncology patients.

Abstract

To the Editor: Parenteral iron replacement therapies are important components of anemia management in chronic kidney disease (CKD) and oncology patients. Anaphylactic reactions have been reported with all parenteral formulations of iron products. Intravenous (IV) iron products are formulated with an iron oxide core surrounded by a carbohydrate shell that stabilizes the iron oxide and slows the release of bioactive iron from the iron oxide core1. Parenteral iron formulations that are available in the US include iron dextran (INFed), sodium ferric gluconate (Ferrlecit), iron sucrose (Venofer), ferric carboxymaltose (Injectafer), and ferumoxytol (Feraheme). These products all share the same basic structure but differ by the size of the core and the surrounding carbohydrate 2. Iron dextran products are composed of dextran polysaccharide, sodium ferric gluconate has a gluconate carbohydrate, iron sucrose has a sucrose carbohydrate, and ferumoxytol has a semi-synthetic carbohydrate surrounding the iron oxide 2. Iron dextran therapy is reported to be associated with a higher incidence of anaphylactic-type reactions (1.7%) than other parenteral iron products; the high rate of anaphylactic reactions reported with iron dextran therapy has been attributed to the high-molecular weight iron dextran (DexFerrum), which is no longer available in the US, and not the low-molecular weight iron dextran (INFed) 2, 3. The reported incidence of ferumoxytol-associated severe hypersensitivity reactions (HSR), anaphylactic, and/or anaphylactoid reactions, is low at < 0.2% 2. Ferumoxytol was FDA approved for the treatment of iron-deficiency anemia in CKD as a single 510 mg dose IV push (undiluted) over ≥ 17 sec followed by a second dose (3–8 days afterwards); patients must be monitored for at least 30 min for HSR. Treatment response is assessed at least 30 days after the second dose, and additional two-dose series may be administered as clinically appropriate. At our institution, ferumoxytol is exclusively used for hematology/oncology patients in an ambulatory cancer center. During the first six months of 2014, an upsurge in the rate and severity of ferumoxytol-associated HSR at our institution prompted a medication usage review at the Chemotherapy Council, and a recommendation was made to routinely administer IV dexamethasone 8 mg prior to each ferumoxytol injection. The objective of our study was to evaluate the incidence and severity of HSR before and after the steroid premedication policy was implemented. A one year, single center, retrospective chart review was performed at The Mount Sinai Hospital (MSH) after obtaining approval from our Institutional Review Board. A data report in the electronic medical record system was run for all patients who received ferumoxytol in the ambulatory cancer center at MSH during the 12-months study period (January to December 2014). Data collection included medical record number, age, gender, known risk factors for drug-induced HSR (age ≥ 60 years, multiple drug allergies, comorbid disease states (asthma or COPD), and concomitant use with a beta blocker, ACE inhibitor, or alpha blocker) 4, number of doses of ferumoxytol given, administration of dexamethasone or other premedications, and any documented HSR reactions to ferumoxytol therapy (severity was graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events V 4.03) 5. Until May 2014, ferumoxytol was administered as 510 mg slow IV push (≥17 sec) without routine premedication as per manufacturer recommendation. From June 2014, dexamethasone 8 mg as IV push was administered prior to each ferumoxytol therapy. Chi-square test was performed to compare the frequencies of incidence between the two groups. A P-value of < 0.05 was considered to have a statistical significance. During the study period, a total of 475 doses of ferumoxytol were administered to 196 patients in the ambulatory cancer center at MSH. The median age of the patients was 50 years (range, 18–93), and patients received a median of two doses (range, 1–11) of ferumoxytol. Of the total of 475 doses of ferumoxytol administered, 230 (48%) were given without steroids and 245 (52%) were given with steroids. There was a significant reduction in both the overall HSR (3.9% vs. 0.4%) and severe HSR (2.2% vs.0%) with the inclusion of steroid premedication (Table 1). Patients who developed severe HSR with symptomatic bronchospasm were managed with emergent administration of IV steroids, IV diphenhydramine, IV famotidine, and inhaled albuterol. The risk factors for HSR present in the two groups are listed in the Supporting Information Table. Compared with those who did not develop HSR, the rates of patients with multiple drug allergies (30% vs. 5.8%; P = 0.002) and asthma (40% vs. 6%; P < 0.001) were significantly higher in patients who developed HSR. There was also a trend toward a higher rate of patients with COPD in the group that developed HSR (10% vs. 1.9%; P = 0.079). Recently, the FDA released 79 post-marketing reports of potentially fatal (18 deaths) ferumoxytol-associated anaphylaxis. As a result, ferumoxytol is now recommended to be administered as an IV infusion over ≥ 15 min 6. The limitations of our study include: (1) The retrospective nature of the study; (2) Patient group was limited to hematology and oncology patients, so it is uncertain whether it would also produce similar outcome in patients with CKD. In summary, our data demonstrated that premedication with a single dose of IV dexamethasone 8 mg effectively reduced the incidence and severity of HSR following ferumoxytol, administered as undiluted IV push over ≥17 sec, in hematology/oncology patients. Authors thank their oncology nursing and pharmacy group at The MSH for addressing ferumoxytol-associated HSR to initiate the investigation. Kara Braaten,1*Randall F. Holcombe,2 and Sara S. Kim3 1Department of Pharmacy, the Mount Sinai Hospital, New York, New York;2Division of Hematology/Oncology, Tisch Cancer Institute, the Mount Sinai Hospital, New York, New York;3Department of Pharmacy, the Mount Sinai Hospital, New York, New York Additional Supporting Information may be found in the online version of this article. Table 1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.