Choice of High-Dose Intravenous Iron Preparation Determines Hypophosphatemia Risk

Abstract

BackgroundFerric 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.AimTo characterize this adverse event and search for its predictors in a gastroenterology clinic patient cohort.MethodsElectronic 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.ResultsThe 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.ConclusionTreatment 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.

Iron deficiency

“…Hypophosphatemia after ferricarboxymaltose is usually transient and reversible, although rarely, severe cases have been reported after repeated infusions. 96 Minor/moderate infusion reactions (nausea, pruritus, urticaria, flushing, back or thoracic pain), often self-limited, may be observed in 1:200 infusions and more serious reactions (hypotension, dyspnea) in 1:200 000. 95 Although globally IV treatment seems safe, the number of reported patients is usually too limited to detect extremely rare anaphylactic reactions, such as those once caused by high molecular weight iron dextran.…”

Symptomatic severe hypophosphatemia after intravenous ferric carboxymaltose

“…In a study of women with a history of heavy uterine bleeding, serum phosphate fell below 0.65 mmol/L in 10 of 25 patients who received FCM compared to none of the 30 women who received iron dextran . In a retrospective study, hypophosphatemia (<0.8 mmol/L) was noted more commonly in the 55 patients who received FCM (45.5%) than in the 26 who received iron isomaltoside (4%) . In a prospective RCT, hypophosphatemia (<0.6 mmol/L) also occurred in 0.4% of 997 patients administered ferumoxytol and 38.7% of 1000 who received FCM .…”

Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial

“…Even mild hypophosphatemia can contribute to osteomalacia over time . A retrospective study showed that hypophosphatemia lasted for ≥2 months in 13 of 17 patients treated with a single dose of FCM, suggesting a persistent hypophosphatemic effect …”