Abstract
Background: Ferric carboxymaltose (Injectafer), a newer intravenous iron agent permits larger iron concentrations to be delivered in fewer doses compared to traditional preparations of intravenous iron. However, ferric carboxymaltose has been shown to up-regulate fibroblast growth factor 23 (FGF23) which can result in severe hypophosphatemia. We present a case illustrating this phenomenon.
Clinical Case: A 48 year-old Caucasian female was admitted to the emergency department with complaints of gradual onset muscle weakness and severe exhaustion. Over the course of several months she noticed significant muscle weakness in all extremities.
Her co-morbidities included morbid obesity (status-post Roux-en-y bypass surgery), asthma, and hereditary angioedema. Due to her history of gastric bypass surgery, the patient required monthly iron sucrose infusions over the previous two years. Her regimen was changed to ferric carboxymaltose (Injectafer) about five months prior to the admission, receiving 750mg treatments twice monthly.
On admission, she was found to have severe hypophosphatemia of 1.5 mg/dL (2.1 – 4.7 mg/dL) with 25-OH vitamin D 21 ng/mL and PTH of 155 pg/mL. A random urinary phosphate was 72 mg/dL with a urine creatinine of 45 mg/dL, with calculated fractional excretion of phosphorus of 74%. Further diagnostic tests including EMG / nerve conduction studies, inflammatory markers, autoimmune workup, and creatine kinase were negative. She was found to have a ferritin of 2159 ng/mL (11 – 306 ng/mL) from previous baseline of 12.8 ng/mL with normal ESR and CRP. This was elucidated to be due to iron overload from IV iron infusions out of proportion to her needs. Therefore, ferrric carboxymaltose was discontinued. Her symptoms gradually improved with phosphorus and vitamin D supplementation. Two months later, when seen by Endocrinology, her ferritin was 1220 ng/mL, PTH 44 pg/mL, and phosphorus normalized to 2.6 mg/dL.
Conclusion: Ferric carboxymaltose can cause profound phosphaturia and hypophosphatemia by inhibiting the cleavage of intact FGF23 to the inactive form, a mechanism similar to autosomal dominant hypophosphatemic rickets. Previous clinical trials show the incidence of hypophosphatemia to be as high as 41-70%. We conclude that baseline phosphorus and vitamin D levels should be obtained prior to therapy and monitored closely during treatment.
Reference: Adkinson NF et al. Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial. Am J Hematol. 2018;93(5):683.
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