Hypophosphatemia Secondary to Iron Infusion

Hypophosphatemia is commonly missed as metabolic panels do not automatically include phosphorus levels and symptoms are nonspecific. Hypophosphatemia can be due to increased renal excretion, decreased intestinal absorption, or intracellular shifts. We report a case of recurrent hypophosphatemia secondary to iron infusion therapy for anemia.

Case Description:

A 41-year-old woman with iron deficiency due to menorrhagia, presented with muscle weakness and myalgia. Due to persistent low ferritin levels ( <10ng/mL 22-322), intravenous (IV) iron dextran, was ordered. After two dosages, her symptoms worsened. Follow-up labs showed a critically low phosphorus level of 0.8 (2.5-5.0 mg/dL). She was seen in the emergency room, given oral phosphorus, and was discharged home. Her symptoms persisted. She returned to the hospital with an undetectable phosphorus level ( <0.1 mg/dL). A review of her chart revealed the iron formulation had been ferric carboxymaltose, not iron dextran. Additional laboratory demonstrated a normal chemistry panel except for hemoglobin 11.1 (12-16 g/dL), corrected calcium 8.2 (8.6-10.3 mg/dL), parathyroid hormone (PTH) 101.2 (12-88 pg/mL). Vitamin D-25-OH was normal at 46.7 (>30 ng/mL). Intravenous and oral phosphorus were administered but low levels persisted. Fractional excretion of phosphorus was 28.27% ( <20%). FGF-23 level was 109 (44-215 RU/mL) following calcitriol administration. While on oral phosphorus (250 mg [8 mmol]/tablet) four times daily and calcitriol 0.25 mcg daily, phosphorus levels remained low at 1.1 mg/dL. Oral phosphorus was increased to six tablets a day (48 mmol/d) and calcitriol to three times a day (0.75 mcg/d). Phosphorus levels improved to 1.8 mg/dL. Three months later, phosphorus and PTH levels normalized to 3.5 mg/dL and 58.4 pg/mL respectively.

Discussion:

Drug-induced hypophosphatemia can result from many medications.1 The case above describes hypophosphatemia induced by ferric carboxymaltose used to treat iron deficiency anemia. Many IV iron formulations have been associated with hypophosphatemia. Hypophosphatemia rates of up to 92.1% are seen with ferric carboxymaltose.2 This formulation increases biologically active FGF-23 levels leading to renal phosphate wasting, calcitriol deficiency, and secondary hyperparathyroidism.3 The duration of hypophosphatemia is 2 to 9 months.4 Overall, hypophosphatemia infrequently requires hospitalization. Still, acutely it can lead to severe weakness and chronically to bone fragility. This case illustrates the importance of medication history, and how understanding the pathophysiology of an adverse drug reaction can lead to successful treatment.