Abstract: FR-OR071

Occurrence of Hypophosphatemia Following IV Iron Treatment: Results from a Randomized Controlled Trial

Session Information

Category: Mineral Disease

  • 1202 Mineral Disease: Vitamin D, PTH, FGF-23

Authors

  • Wolf, Myles S., Duke University, Durham, North Carolina, United States
  • Strauss, William, AMAG Pharmaceuticals, Inc., Waltham, Massachusetts, United States
  • Bernard, Kristine, AMAG Pharmaceuticals, Inc., Waltham, Massachusetts, United States
  • Dahl, Naomi V., AMAG Pharmaceuticals, Inc., Waltham, Massachusetts, United States
  • Kaper, Robert F., AMAG Pharmaceuticals, Inc., Waltham, Massachusetts, United States
  • Krop, Julie S, AMAG Pharmaceuticals, Inc., Waltham, Massachusetts, United States
Background

Hypophosphatemia is a common complication of administration of certain IV irons. For example, 32.1% of patients with gastrointestinal disorders who received treatment with ferric carboxymaltose (FCM) developed hypophosphatemia, <0.6 mmol/L (1.9 mg/dl) (Schaefer et al., PLoS ONE 2016). Acute increases in circulating levels of intact fibroblast growth factor 23 (FGF23) mediate hypophosphatemia due to renal phosphate wasting in response to FCM, but not iron dextran, suggesting that the specific carbohydrate moieties might be involved in the differential FGF23 response to IV iron (Wolf et al., Bone Min Res, 2013). While initially considered a transient and benign laboratory finding, reports are accumulating of significant clinical sequelae associated with chronic FCM-associated hypophosphatemia.

Methods

In a large RCT (NCT02694978) that compared the safety and efficacy of standard courses of ferumoxytol (FER, 510mg x 2 doses; N=997), vs. FCM (750mg x 2 doses; N=1000) in patients with iron deficiency anemia of any etiology except dialysis-dependent CKD, we measured serum phosphate and fractional excretion of phosphate (FEPi) at baseline, day 8 (prior to dose 2), week 2 and week 5.

Results

Mean baseline serum phosphate was 1.22 mmol/L (3.8 mg/dl) and FEPi was 15.7% in both groups. Among patients receiving FCM, serum phosphate decreased significantly, and FEPi increased significantly at all time points compared to ferumoxytol-treated patients (P<0.0001; Figure). Serum phosphate <0.6 mmol/L (1.9 mg/dl) occurred in 38.7% of FCM patients, and only 0.4% of FER patients.

Conclusion

FCM induced a marked drop in blood phosphorus occurring as soon as 8 days following 750mg of FCM secondary to a significant increase in FEPi. Almost 40% of patients developed at least moderate hypophosphatemia. These changes did not occur following FER.

Funding

  • Commercial Support