Efficacy and Safety of Intravenous Ferric Carboxymaltose in Children with Iron Deficiency Anemia Unresponsive to Oral Iron Therapy
Authors: Powers Jacquelyn M. , Shamoun Mark P. , McCavit Timothy L. , Adix Leah , Buchanan George R. 
Published: October 2019

Abstract

Background
The standard first line therapy for iron deficiency anemia (IDA) is oral iron. Yet, many patients fail to respond to oral iron due to poor adherence and/or adverse effects. Intravenous (IV) iron is an effective means of treating IDA in patients with malabsorption of iron or who are non-adherent and/or experience adverse effects with oral iron. Some IV iron preparations carry an FDA-mandated black box warning and/or require a test dose or prolonged infusion. Ferric carboxymaltose (FCM, Injectafer®) is a relatively new IV iron preparation with demonstrated safety and efficacy in adults with IDA. The manufacturer recommended dosing is 15 mg/kg/dose (maximum 750 mg) x2 doses administered at least 7 days apart, and each individual infusion can be administered over 10 to 15 minutes, without the need for a test dose. Limited data exist on its use in children. Our objective was to assess the hematologic response and adverse effects of IV FCM in a diverse population of infants, children and adolescents with IDA who failed oral iron therapy.
Method
All children with IDA who received FCM at Children's Health from June 1, 2014 through June 10, 2015 were included. Subjects were identified via search of pharmacy records. All patients received at least one dose of FCM 15 mg/kg (maximum 750 mg) administered as a 15-minute IV infusion (without test dose or pre-medications). Patient characteristics, adverse effects and hematologic response were retrospectively collected from the electronic medical record.
Results
During the study frame, one hundred twenty-five infusions of FCM were administered to 87 patients (71% female) with a median age of 14 years (range 9 months to 20.8 years). The most common racial/ethnic group was Caucasian/White (Latino) at 45% followed by African American/Black and Caucasian/White (Non-Latino), each at 22%. The primary etiologies were heavy menstrual bleeding (38%), nutritional (24%), and GI bleeding and/or malabsorption (20%) with the remaining 18% representing other/mixed causes of IDA (e.g., inflammatory).
The median dose administered during a single infusion was 750 mg (range 132 to 750 mg). No adverse effects were noted during or following the infusion in 77 subjects. Two patients had transient tingling, nausea and/or mild abdominal pain. Five others developed generalized pruritis and/or urticaria and received diphenhydramine and/or hydrocortisone, with prompt resolution. Two adolescents had more clinically significant reactions, 1 with nausea/vomiting post-infusion (likely psychogenic) requiring admission, and 1 with dyspnea 2 minutes into the infusion, requiring its immediate termination and administration of diphenhydramine, hydrocortisone and normal saline with prompt symptom resolution. One patient experienced asymptomatic extravasation during the second infusion which resulted in localized iron-staining of the skin.
Median pre-infusion hemoglobin concentration for all patients was 9.1 g/dL (range 3.9 to 13.3 g/dL) (Table). A follow-up measurement was available for 76 patients at a median time of 6 weeks (range 1 to 30 weeks) post-initial infusion with a median hemoglobin increase of 3.3 g/dL (range -1.5 to 9.5 g/dL).
Conclusion
Intravenous FCM, administered in an outpatient infusion setting as one or two short IV infusions and without need for a test dose, was safe and effective in most children and adolescents with IDA refractory to oral iron therapy. Further clinical data are necessary to more fully characterize the extent of adverse effects in young patients. Prospective studies of IV FCM in children are indicated to assess clinical efficacy, including outcomes such as health related quality of life and fatigue.
Table. *Hematologic Response to FCM Pre-Infusion **Post-Infusion Hemoglobin concentration (g/dL) All Etiologies, Pre (n=87), Post (n=76) Heavy menstrual bleeding, Pre (n=33), Post (n=26) Nutritional, Pre (n=21), Post (n=20) - 9.1 (3.9 to 13.3) 9.3 (4.2 to 13.3) 8.8 (4.9 to 12.2) - 12.2 (7.1 to 16) 12.7 (8.8 to 16) 12.2 (10.5 to 13.7) Mean corpuscular volume (fl), Pre (n=87), Post (n=76) 71.6 (49.5 to 97.4) 80.9 (53.3 to 102) Serum ferritin (ng/mL), Pre (n=80), Post (n=60) 5.2 (0.6 to 288.6) 115.7 (2.3 to 679.3) *Median laboratory values are reported. **Follow-up laboratory testing occurred at median time of 6 weeks (range 1 to 30 weeks) post-infusion.

Disclosures
Powers: Gensavis Pharmaceuticals, LLC: Research Funding. McCavit:Pfizer: Research Funding; Gensavis LLC: Research Funding; Novartis: Speakers Bureau. Adix:Gensavis Pharmaceuticals, LLC: Research Funding. Buchanan:Gensavis Pharmaceuticals, LLC: Research Funding.