Experience with Intravenous Ferric Carboxymaltose in Patients with Iron Deficiency Anemia

Erythropoiesis may be limited by absolute or functional iron deficiency
or when chronic inflammatory conditions lead to iron sequestration.
Intravenous iron may be indicated when oral iron cannot address the
deficiency. Ferric carboxymaltose (FCM) is a nondextran iron preparation
recently approved in the United States for intravenous treatment of
iron deficiency anemia (IDA) in adult patients with intolerance or
unsatisfactory response to oral iron or with nondialysis-dependent
chronic kidney disease. The full dose is two administrations of up to
750 mg separated by at least 7 days (up to 1500 mg total). FCM can be
injected in 7-8 min or diluted in saline for slower infusion. The
efficacy and safety of this dose was established in two prospective
trials that randomized over 3500 subjects, 1775 of whom received FCM.
One trial showed similar efficacy of FCM to an approved intravenous iron
regimen (1000 mg of iron sucrose) in 2500 subjects with chronic kidney
disease and additional cardiovascular risk factors. The other trial
showed superior efficacy of FCM to oral iron in subjects with IDA due to
various etiologies (e.g. gastrointestinal or uterine bleeding). In
these trials, there was no significant difference between FCM and
comparator with respect to an independently adjudicated composite safety
endpoint, including death, myocardial infarction, or stroke. A database
of 5799 subjects exposed to FCM provided a safety profile acceptable
for regulatory approval. Mechanistic studies demonstrated that the
transient, asymptomatic reduction in serum phosphate observed following
FCM administration results from induction of fibroblast growth factor
23, which in turn induces renal phosphate excretion. An elevated
hepcidin level may identify patients with IDA who will not respond to
oral iron but will respond to FCM. The ability to administer FCM in two
rapid injections or infusions will likely be viewed favorably by
patients and healthcare providers.