Choice of High-Dose Intravenous Iron Preparation Determines Hypophosphatemia Risk

PLoS One. 2016 Dec 1;11(12):e0167146. doi: 10.1371/journal.pone.0167146. eCollection 2016.


Background: Ferric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) are increasingly used because they allow correction of severe iron deficiency in a single infusion. A transient decrease in serum phosphate concentrations is a frequent side effect of FCM.

Aim: To characterize this adverse event and search for its predictors in a gastroenterology clinic patient cohort.

Methods: Electronic medical records of patients attending the University Hospital of Innsbruck were searched for the keywords ferric carboxymaltose or iron isomaltoside. Eighty-one patients with documented administration of FCM or IIM with plasma phosphate concentrations before and after treatment were included.

Results: The prevalence of hypophosphatemia (<0.8 mmol/L) increased from 11% to 32.1% after treatment with i.v. iron. The hypophosphatemia risk was greater after FCM (45.5%) compared with IIM (4%). Severe hypophosphatemia (<0.6 mmol/L) occurred exclusively after FCM (32.7%). The odds for hypophosphatemia after i.v. iron treatment were independently determined by baseline phosphate and the choice of i.v. iron preparation (FCM vs. IIM-OR = 20.8; 95% CI, 2.6-166; p = 0.004). The median time with hypophosphatemia was 41 days, but prolonged hypophosphatemia of ≥ 2 months was documented in 13 of 17 patients in whom follow-up was available. A significant increase in the phosphaturic hormone intact FGF-23 in hypophosphatemic patients shows that this adverse event is caused by FCM-induced hormone dysregulation.

Conclusion: Treatment with FCM is associated with a high risk of developing severe and prolonged hypophosphatemia and should therefore be monitored. Hypophosphatemia risk appears to be substantially lower with IIM.

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Anemia, Iron-Deficiency / complications*
  • Anemia, Iron-Deficiency / diagnosis
  • Anemia, Iron-Deficiency / drug therapy
  • Anemia, Iron-Deficiency / etiology
  • Biomarkers
  • Disaccharides / administration & dosage
  • Disaccharides / adverse effects
  • Female
  • Ferric Compounds / administration & dosage
  • Ferric Compounds / adverse effects*
  • Fibroblast Growth Factor-23
  • Humans
  • Hypophosphatemia / diagnosis
  • Hypophosphatemia / epidemiology
  • Hypophosphatemia / etiology*
  • Male
  • Maltose / administration & dosage
  • Maltose / adverse effects
  • Maltose / analogs & derivatives
  • Middle Aged
  • Phosphates / blood
  • Prevalence
  • Retrospective Studies
  • Risk


  • Biomarkers
  • Disaccharides
  • FGF23 protein, human
  • Ferric Compounds
  • Phosphates
  • iron isomaltoside 1000
  • ferric carboxymaltose
  • Maltose
  • Fibroblast Growth Factor-23

Grants and funding

The study was funded by the Medical University of Innsbruck and the Medical Research Council. Benedikt Schaefer received a grant from the “Verein zur Foerderung der Wissenschaft in Gastroenterologie & Hepatologie.” The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.