Hypophosphatemia after Treatment of Iron Deficiency with Intravenous
Ferric Carboxymaltose or Iron Isomaltoside - A Systematic Review and
Meta-Analysis
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. 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.