Br J Clin Pharmacol. 2020 Nov 13. doi: 10.1111/bcp.14643. Online ahead of print.

Benedikt Schaefer ^1 2, Moritz Tobiasch ³, André Viveiros ^1 2, Herbert Tilg ¹, Nicholas A Kennedy ^4 5, Myles Wolf ⁶, Heinz Zoller ^1 2

Author information

• ¹Medical University of Innsbruck, Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Innsbruck, Austria.
• ²Christian Doppler Laboratory of Iron and Phosphate Biology, Medical University of Innsbruck.
• ³University Teaching Hospital of Hall in Tirol, Department of Medicine, Hall, Austria.
• ⁴University of Exeter, IBD Pharmacogenetics, University of Exeter, Exeter, United Kingdom.
• ⁵Gastrointestinal Unit, Western General Hospital, Edinburgh, United Kingdom.
• ⁶Department of Medicine, Division of Nephrology, and Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, United States of America.

Abstract

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. The aim of this study was 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.