Ferric carboxymaltose

The iron complex ferric carboxymaltose is designed to provide, in a controlled way, utilisable iron for the iron transport and storage proteins in the body (transferrin and ferritin, respectively).

Red cell utilisation of ⁵⁹Fe from radio-labelled ferric carboxymaltose ranged from 91% to 99% in subjects with iron deficiency (ID) and 61% to 84% in subjects with renal anaemia at 24 days post-dose.

Ferric carboxymaltose treatment results in an increase in reticulocyte count, serum ferritin levels and TSAT levels to within normal ranges.

Distribution

Positron emission tomography demonstrated that ⁵⁹Fe and ⁵²Fe from ferric carboxymaltose was rapidly eliminated from the blood, transferred to the bone marrow, and deposited in the liver and spleen.

After administration of a single dose of ferric carboxymaltose of 100 to 1,000 mg of iron in ID subjects, maximum total serum iron levels of 37 µg/mL up to 333 µg/mL are obtained after 15 minutes to 1.21 hours respectively. The volume of the central compartment corresponds well to the volume of the plasma (approximately 3 litres).

Elimination

The iron injected or infused was rapidly cleared from the plasma, the terminal half-life ranged from 7 to 12 hours, the mean residence time (MRT) from 11 to 18 hours. Renal elimination of iron was negligible.

Preclinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeat dose toxicity and genotoxicity. Preclinical studies indicate that iron released from ferric carboxymaltose does cross the placental barrier and is excreted in milk in limited, controlled amounts. In reproductive toxicology studies using iron replete rabbits ferric carboxymaltose was associated with minor skeletal abnormalities in the fetus. In a fertility study in rats, there were no effects on fertility for either male or female animals. No long-term studies in animals have been performed to evaluate the carcinogenic potential of ferric carboxymaltose. No evidence of allergic or immunotoxic potential has been observed. A controlled in-vivo test demonstrated no cross-reactivity of ferric carboxymaltose with anti-dextran antibodies. No local irritation or intolerance was observed after intravenous administration.