Abstract
An ideal preparation for intravenous iron replacement therapy should balance effectiveness
and safety. Compounds that release iron rapidly tend to cause toxicity, while large
molecules can induce antibody formation and cause anaphylactic reactions. There is
therefore a need for an intravenous iron preparation that delivers appropriate amounts
of iron in a readily available form but with minimal side effects and thus with an
excellent safety profile. In this paper, a review is given on the chemistry, pharmacology,
and toxicology of ferric carboxymaltose (FCM, Ferinject®), a stable and robust complex
formulated as a colloidal solution with a physiological pH.
The complex is gradually taken up mainly from the hepatic reticulo-endo-thelial system
(RES), followed by effective delivery of iron to the endogeneous transport system
for the haem synthesis in new erythrocytes, as shown in studies on the pharmacodynamics
and pharmacokinetics with radio-labelled FCM. Studies with radio-labelled FCM also
demonstrated a barrier function of the placenta and a low transfer of iron into the
milk of lactating rats. Safety pharmacology studies indicated a favourable profile
with regard to cardiovascular, central nervous, respiratory, and renal toxicity. A
high maximum non-lethal dose was demonstrated in the single-dose toxicity studies.
Furthermore, based on the No-Observed-Adverse-Effect-Levels (NOAELs) found in repeated-dose
toxicity studies and on the cumulative doses administered, FCM has good safety margins.
Reproductive and developmental toxicity studies did not reveal any direct or indirect
harmful effects. No genotoxic potential was found in in vitro or in vivo studies. Moreover, antigenicity studies showed no cross-reactivity of FMC with anti-dextran
antibodies and also suggested that FCM does not possess sensitizing potential. Lastly,
no evidence of irritation was found in local tolerance studies with FCM.
This excellent toxicity profile and the high effectiveness of FCM allow the administration
of high doses as a single infusion or bolus injection, which will enhance the cost-effectiveness
and convenience of iron replacement therapy. In conclusion, FCM has many of the characteristics
of an ideal intravenous iron preparation.
Key words
Anaemia - Ferinject® - Ferric carboxymaltose, chemistry, pharmacology, toxicology
- Intravenous iron - Iron deficiency
