FDA adds boxed warning to ferric carboxymaltose for serious hypophosphatemia

Clinical takeaway: Check serum phosphate before repeat ferric carboxymaltose treatment in at-risk patients and anyone receiving another course within three months. Correct pre-existing hypophosphatemia, counsel patients about symptoms, and consider permanent discontinuation for severe symptomatic or persistent cases.

Fatigue and muscle weakness after intravenous iron may be mistaken for persistent iron deficiency anemia. FDA is drawing greater attention to another possible cause: symptomatic hypophosphatemia associated with ferric carboxymaltose injection.

FDA has added a boxed warning about the risk to the labeling for Injectafer (ferric carboxymaltose).

The risk is not newly recognized. FDA added an initial warning in 2020 and strengthened monitoring recommendations in 2023, but symptomatic cases continued to be reported. FDA Sentinel data showed that serum phosphate testing occurred in fewer than 20% of ferric carboxymaltose administration episodes.

Cases have occurred after both single and multiple infusions, although serious postmarketing cases have been reported mostly after repeated exposure. Consequences have included hospitalization, prolonged phosphate replacement, osteomalacia, and fractures.

Before treatment, clinicians should review risk factors such as gastrointestinal malabsorption, inflammatory bowel disease, vitamin D deficiency, malnutrition, hyperparathyroidism, hereditary hemorrhagic telangiectasia, and medications that affect proximal renal tubular function. Correct existing hypophosphatemia before administering the drug and monitor patients at risk for chronically low phosphate.

Counsel patients to report new or worsening fatigue, muscle weakness or pain, bone or joint pain, tremors, confusion, seizures, or symptoms of cardiac arrhythmia. Treat hypophosphatemia as clinically indicated and consider permanently discontinuing ferric carboxymaltose when hypophosphatemia is severe and symptomatic or does not resolve.

Source: FDA. (2026 Sep 1). FDA adds boxed warning to labeling for ferric carboxymaltose injection (Injectafer) to describe risk of low phosphate levels