EMA investigates injectable iron medicines for severe bone complications
The European Medicines Agency's Pharmacovigilance Risk Assessment Committee has launched a safety review of all injectable iron medicines following reports of severe hypophosphatemia and osteomalacia. The review evaluates risks across formulations like ferric carboxymaltose, which clinical trials show has a higher rate of phosphate reduction than other treatments. Diagnosis is often delayed because symptoms overlap with iron deficiency and osteomalacia may not appear on standard x-rays.
Injectable iron safety review
▪The European Medicines Agency's Pharmacovigilance Risk Assessment Committee launched a safety review across all injectable iron formulations on September 7, 2026.
▪The European Medicines Agency's safety review excludes oral iron supplements because they provide lower iron amounts and carry a lower risk for hypophosphatemia.
▪The European Medicines Agency's safety review was prompted by reports of severe hypophosphatemia and osteomalacia linked to injectable iron medicines.
Hypophosphatemia bone complications
▪Injectable iron medicines are used to treat iron deficiency and iron-deficiency anemia when oral supplements are inadequate, not tolerated, or too slow.
▪Hypophosphatemia is a recognized adverse effect of ferric carboxymaltose, affecting up to 1 in 10 patients, but the frequency of hypophosphatemia-related osteomalacia remains unknown.
▪Reports of osteomalacia linked to injectable iron medicines have occurred after only one or two doses and in patients with no recognized risk factors.
Diagnostic symptom overlap
▪Osteomalacia caused by injectable iron medicines may not be visible on standard x-rays, further complicating timely diagnosis.
▪Symptoms of low phosphate, such as fatigue, muscle pain, and bone pain, overlap with underlying iron deficiency symptoms, potentially delaying diagnosis.
Ferric carboxymaltose evidence
▪A systematic review and meta-analysis found that hypophosphatemia persisted through study end points in up to 45% of patients treated with ferric carboxymaltose.
▪A systematic review and meta-analysis of 42 clinical trials found hypophosphatemia occurred in 47% of patients treated with ferric carboxymaltose compared to 4% with iron isomaltoside.
▪Preserved kidney function and markers of severe iron deficiency, including low baseline ferritin and transferrin saturation, were identified as significant predictors of hypophosphatemia.
PRAC regulatory assessment
▪The Pharmacovigilance Risk Assessment Committee will assess whether the risks of hypophosphatemia affect the overall benefit-risk balance of injectable iron medicines.
▪The final recommendations of the Pharmacovigilance Risk Assessment Committee will be forwarded to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human.
▪The Pharmacovigilance Risk Assessment Committee's evaluation includes injectable medicines containing ferric carboxymaltose, ferric derisomaltose, iron dextran, ferric gluconate, ferric hydroxide polymaltose complex, and iron sucrose.
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