Symptomatic hypophosphataemia after intravenous iron therapy: an underrated adverse reaction

Abstract

Summary Iron (ferric carboxymaltose) infusion therapy is used to treat severe iron deficiency which is not responding to the first-line oral iron therapy. However, it can also cause severe renal wasting of phosphate resulting in severe hypophosphataemia in some patients. Despite the growing number of case reports, this side effect is not well known to healthcare professionals. The product labelling information sheet does mention that hypophosphataemia can be a side effect, but also says that this side effect is usually transient and asymptomatic. We report a challenging case of a patient who developed severe, symptomatic and prolonged hypophosphataemia after an intravenous iron infusion for severe iron deficiency. Learning points: Clinicians prescribing ferric carboxymaltose (Ferinject®) should be aware of the common side effect of hypophosphataemia, which could be mild, moderate or severe. Patients receiving iron infusion should be educated concerning this potential side effect. Pre-existing vitamin D deficiency, low calcium levels, low phosphate levels or raised parathyroid hormone levels may be risk factors, and these should be evaluated and corrected before administering intravenous iron. Patients may require phosphate and vitamin D replacement along with monitoring for a long period after iron infusion-induced hypophosphataemia. Every incident should be reported to the designated body so that the true prevalence and management thereof can be ascertained.

Anaemia in cardiac surgery – a retrospective review of a centre's experience with a pre‐operative intravenous iron clinic

“…iron with erythropoiesis‐stimulating agents, there are no prospective studies showing an increased risk of infection, while others suggest the opposite [25], and current data are conflicting. Finally, the use of ferric carboxymaltose (Ferinject, Vifor Pharma, Glattbrug, Switzerland) has been associated with varying degrees of hypophosphataemia secondary to increased renal losses [26]. While, in the majority of patients, this is transient and asymptomatic, patients with pre‐existing hypocalcaemia, hypophosphataemia, low vitamin D levels or elevated parathyroid hormone levels may be at increased risk.…”

Incidence of Hypophosphatemia after Ferric Carboxymaltose Treatment: Single Center Experience

“…Although hypophosphatemia related to FCM has been defined as mostly asymptomatic in randomized controlled studies, cases with severe hypophosphatemia, cramps, dizziness, fatigue, nausea, and requiring long-term hospitalization have been reported in the acute period 14,15,18 . In addition, hypophosphatemic osteomalacia and related fractures have been reported in patients receiving repeated doses of therapy in recent years.…”

Newer formulations of intravenous iron: a review of their chemistry and key safety aspects – hypersensitivity, hypophosphatemia, and cardiovascular safety

“…In the headto-head trials described earlier, severe hypophosphatemia was observed following treatment with FCM, but not with FDI [28] or FER [49]. Although these trials did not report on related symptoms, numerous isolated patient reports describing acute symptomatic hypophosphatemia following treatment with FCM have been published [68][69][70][71][72][73]. In a review paper published in 2017, Zoller et al discussed the long-term complications of hypophosphatemia following IV iron treatment, such as bone fractures and osteomalacia [44].…”