The FDA approved a label change for ferric carboxymaltose injection (Injectafer) that adds a boxed warning for the risk of symptomatic hypophosphatemia.
The agency recommends monitoring of phosphate levels in patients at risk for hypophosphatemia and in any patient who receives a repeat course of therapy within 3 months of the prior course.
Ferric carboxymaltose is an iron replacement therapy. Originally approved in 2013, the intravenously delivered drug carries indications for treating iron deficiency anemia in patients 1 year and older who cannot tolerate or don’t fully respond to oral iron; in adults who have non-dialysis-dependent chronic kidney disease; and in adults with heart failure and New York Heart Association class II/III to improve exercise capacity.
The FDA had already made labeling changes for ferric carboxymaltose injection in February 2020 and May 2023, adding and strengthening the warning about the risk of hypophosphatemia, respectively.
However, an assessment this year found that symptomatic hypophosphatemia continues to be reported with ferric carboxymaltose injection. An FDA Adverse Event Reporting System case series included reports of symptomatic hypophosphatemia that occurred after both single and multiple infusions of ferric carboxymaltose injection and resulted in hospitalizations, the need for phosphate replacement therapy over weeks to months, and extensive monitoring with regular follow-up medical visits.
Chronic hypophosphatemia associated with ferric carboxymaltose can also lead to osteomalacia (bone softening) and fractures, and the agency suggested that these serious adverse reactions can be prevented or reduced in severity through appropriate phosphate level monitoring and early intervention.
The FDA advised patients to report any new or worsening symptoms of low phosphate levels — which can include muscle weakness or pain, fatigue, bone and joint pain, tremors, confusion, or cardiac arrhythmias — to their healthcare provider.
In turn, providers should inform patients about the risk for hypophosphatemia with ferric carboxymaltose injection use. They should also correct pre-existing hypophosphatemia prior to administering the drug, treat hypophosphatemia as medically indicated, and consider permanent discontinuation of ferric carboxymaltose for severe symptomatic hypophosphatemia or persistent hypophosphatemia.
