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Hypophosphatemia after Treatment of Iron Deficiency with Intravenous Ferric Carboxymaltose or Iron Isomaltoside - A Systematic Review and Meta-Analysis
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  • Benedikt Schaefer,
  • Moritz Tobiasch,
  • André Viveiros,
  • Herbert Tilg,
  • Nicholas A Kennedy,
  • Myles Wolf,
  • Heinz Zoller
Benedikt Schaefer
Medical University of Innsbruck,

Corresponding Author:[email protected]

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Moritz Tobiasch
University Teaching Hospital of Hall in Tirol
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André Viveiros
Medical University of Innsbruck
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Herbert Tilg
Medical University of Innsbruck
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Nicholas A Kennedy
University of Exeter
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Myles Wolf
Duke University
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Heinz Zoller
Medical University of Innsbruck
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Aims: Hypophosphatemia is an increasingly recognized side-effect of ferric carboxymaltose (FCM) and possibly iron isomaltoside/ferric derisomaltose (IIM), which are used to treat iron deficiency. To determine frequency, severity, duration and risk factors of incident hypophosphatemia after treatment with FCM and IIM. Methods: A systematic literature search for articles indexed in EMBASE, PubMed and Web of Science in years 2005 to 2020 was carried out using the search terms ‘ferric carboxymaltose’ OR ‘iron isomaltoside’. Prospective clinical trials reporting outcomes on hypophosphatemia rate, mean nadir serum phosphate and/or change in mean serum phosphate from baseline were selected. Hypophosphatemia rate and severity were compared for studies on IIM vs. FCM after stratification for chronic kidney disease. Meta-regression analysis was used to investigate risk factors for hypophosphatemia. Results: Across the 42 clinical trials included in the meta-analysis, FCM induced a significantly higher incidence of hypophosphatemia than IIM (47%, 95% CI 36-58% vs. 4%, 95% CI 2-5%), and significantly greater mean decreases in serum phosphate (0.40 versus 0.06 mmol/L). Hypophosphatemia persisted at the end of the study periods (maximum 3 months) in up to 45% of patients treated with FCM. Meta-regression analysis identified low baseline serum ferritin and transferrin saturation, and normal kidney function as significant predictors of hypophosphatemia. Conclusion: FCM is associated with a high risk of hypophosphatemia, which does not resolve for at least 3 months in a large proportion of affected patients. More severe iron deficiency and normal kidney function are risk factors for hypophosphatemia.
01 Sep 2020Submitted to British Journal of Clinical Pharmacology
03 Sep 2020Submission Checks Completed
03 Sep 2020Assigned to Editor
04 Sep 2020Reviewer(s) Assigned
10 Sep 2020Review(s) Completed, Editorial Evaluation Pending
22 Oct 2020Editorial Decision: Revise Minor
27 Oct 20201st Revision Received
28 Oct 2020Submission Checks Completed
28 Oct 2020Assigned to Editor
28 Oct 2020Review(s) Completed, Editorial Evaluation Pending
03 Nov 2020Editorial Decision: Accept