Other safety alerts
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| The United States: FDA adds Boxed Warning to labeling for Ferric Carboxymaltose Injection (Injectafer) to describe risk of low phosphate levels |
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What is FDA Doing?
The Food and Drug Administration (FDA) has approved revisions to the labeling for ferric carboxymaltose injection (currently marketed as Injectafer) that adds a boxed warning, the agency’s most prominent safety warning. This boxed warning describes the risk for symptomatic hypophosphatemia (low levels of phosphate in the blood) associated with ferric carboxymaltose injection and recommends phosphate monitoring in patients at risk of hypophosphatemia and in any patient who receives a repeat course of therapy within three months of the prior course.
Clinical manifestations depend on the severity and duration of hypophosphatemia. Symptoms may include muscle weakness or pain, fatigue, tremors, confusion, seizures, and cardiac arrhythmias. Chronic severe hypophosphatemia may lead to osteomalacia (bone softening) and bone fractures.
FDA has previously approved other labeling updates for Injectafer that describe this risk. In 2019, FDA determined that ferric carboxymaltose injection can cause serious symptomatic hypophosphatemia. As a result, in February 2020, FDA approved labeling revisions that, along with other changes, added a warning about this risk. In 2023, the warning was revised to include recommendations for serum phosphate level monitoring in patients at risk for hypophosphatemia and in any patient who receives a repeat course of treatment within three months. The revised warning also included osteomalacia and fractures as potential long-term complications and added inflammatory bowel disease as a possible risk factor for hypophosphatemia. In 2025, the warning was further revised to include additional risk factors for hypophosphatemia.
In 2026, FDA conducted an assessment of hypophosphatemia in association with ferric carboxymaltose injection using multiple data sources, including the FDA Adverse Event Reporting System (FAERS) database (which has been incorporated into the FDA Adverse Event Monitoring System [AEMS] database), literature reports, and FDA’s Sentinel System. FDA found that symptomatic hypophosphatemia continues to be reported with ferric carboxymaltose injection and serum phosphate testing levels are low despite labeling changes in February 2020 and May 2023.
What Is Ferric Carboxymaltose Injection (Injectafer)?
Ferric carboxymaltose injection (Injectafer) is a prescription iron replacement medicine originally approved in 2013 to treat iron deficiency anemia. Ferric carboxymaltose injection is given intravenously (through the vein). Iron deficiency anemia is a common type of anemia that can cause fatigue, weakness, shortness of breath, and other symptoms. Injectafer is approved for patients one year of age and older who cannot tolerate or do not fully respond to oral iron. It is also approved for iron deficiency in adults who have non-dialysis-dependent chronic kidney disease, and for iron deficiency in adults with heart failure and New York Heart Association class II/III to improve exercise capacity. Certain strengths of Injectafer are also approved as ferric carboxymaltose injection generic products. Generic application holders are expected to update their labeling to incorporate this change after this approval.
What Should Patients Do?
Patients should immediately report any new or worsening symptoms of low phosphate levels (e.g., muscle weakness or pain, fatigue, bone and joint pain, confusion) to their healthcare provider. Some of these symptoms may mimic those of iron deficiency anemia.
What Should Healthcare Providers Do?
Healthcare providers should inform patients of the risk of hypophosphatemia with ferric carboxymaltose injection use. Healthcare providers should also:
- Check serum phosphate levels prior to a repeat course of treatment if the patient is at risk for low serum phosphate or if the patient will receive a repeat course of therapy within three months of the prior course.
- Correct pre-existing hypophosphatemia prior to administering Injectafer.
- Monitor serum phosphate levels in patients at risk for chronic low serum phosphate.
- Treat hypophosphatemia as medically indicated.
- Consider permanent discontinuation of Injectafer for severe symptomatic hypophosphatemia or persistent hypophosphatemia.
What Did FDA Find?
FDA found that symptomatic hypophosphatemia continues to be reported with ferric carboxymaltose injection, despite labeling changes in February 2020 and May 2023 adding and strengthening the warning about this risk. The FAERS case series included reports of symptomatic hypophosphatemia that occurred after both single and multiple infusions of ferric carboxymaltose injection. Consequences included hospitalization, need for phosphate replacement therapy over weeks to months, and extensive monitoring with regular follow-up medical visits.
Data from the FDA’s Sentinel System indicate that serum phosphate laboratory testing occurs in fewer than 20% of ferric carboxymaltose administration episodes.
Hypophosphatemia associated with ferric carboxymaltose can lead to serious outcomes including hospitalization, a need for prolonged phosphate replacement therapy, osteomalacia, and fractures. This serious adverse reaction can be prevented or reduced in severity through appropriate phosphate level monitoring and early intervention. Therefore, FDA has required a boxed warning be added to the Injectafer labeling describing the risk for symptomatic hypophosphatemia and recommending mitigation strategies. This action highlights the warning already in the Injectafer labeling.
Please refer to the following website in FDA for details:
http://www.fda.gov/drugs/drug-safety-communications/fda-adds-boxed-warning-labeling-ferric-carboxymaltose-injection-injectafer-describe-risk-low
In Hong Kong, there are 2 registered pharmaceutical products containing ferric carboxymaltose and are prescription-only medicines. So far, the Department of Health (DH) has received one case of adverse drug reaction with regard to ferric carboxymaltose, but the case was not related to hypophosphatemia.
Related news was previously issued by Australia Therapeutic Goods Administration and the United Kingdom Medicines and Healthcare products Regulatory Agency, and was posted on the Drug Office website on 28 Feb 2020 and 17 Nov 2020. Letters to inform local healthcare professionals were issued by DH on 28 Feb 2020. In Dec 2020, the Registration Committee of the Pharmacy and Poisons Board of Hong Kong discussed the matter and decided that the sales pack label and/or package insert of registered ferric carboxymaltose injection products should include safety information about the risk of hypophosphatemia and hypophosphatemic osteomalacia, and serum phosphate should be monitored in patients with existing risk factors for hypophosphataemia and those who receive multiple administrations at higher doses or long-term treatment. DH will remain vigilant on safety update of the drug issued by other overseas drug regulatory authorities.
Ends/Wednesday, Sep 2, 2026
Issued at HKT 15:45
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