Hypophosphatemia after Treatment of Iron Deficiency with Intravenous
Ferric Carboxymaltose or Iron Isomaltoside -A Systematic Review and
Meta-Analysis
Abstract
Background: 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. Objective:
To determine frequency, severity, duration and risk factors of incident
hypophosphatemia after treatment with FCM and IIM. Data Sources: 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’. Study Selection:
Prospective clinical trials reporting outcomes on hypophosphatemia rate,
mean nadir serum phosphate and/or change in mean serum phosphate from
baseline were selected. Data Extraction: 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.
Interpretation: 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.