Pharmacokinetics, pharmacodynamics, safety, and tolerability of intravenous ferric carboxymaltose: a dose-escalation study in Japanese volunteers with iron-deficiency anemia.

Iron-deficiency anemia (IDA) is the most common form of anemia. Iron replacement therapy is an effective treatment, but oral and previously available intravenous (IV) formulations in Japan have disadvantages such as side effects, immunogenic reactions, low dose per tablet/vial, and the need for continuous administration. Ferric carboxymaltose (FCM), which overcomes these limitations, is widely used as an IV iron preparation outside of Japan. In this single-center, open-label, single-dose escalation study, we investigated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of FCM in Japanese subjects. Twenty-four Japanese IDA patients, diagnosed by hemoglobin, serum ferritin, and transferrin saturation, were assigned in equal groups to the 100, 500, 800, and 1000 mg iron dose arms. All subjects completed the study without important protocol deviations. Mean total serum iron concentrations showed a rapid, dose-dependent increase after FCM injection, reaching a maximum within 1 h. Mean reticulocyte counts significantly increased in all arms, suggesting improved hematopoietic function. Fourteen of 24 subjects experienced adverse events, but these were neither serious nor led to drug interruption. The PK/PD and safety profiles were similar in Japanese and European subjects. Ferric carboxymaltose is safe for administration in Japanese patients with IDA.