Iron (III) isomaltoside

Iron(III) complex enables a controlled and slow release of bioavailable iron to iron-binding proteins with little risk of free iron.

Evidence of a therapeutic response can be seen within a few days of administration of iron(III) as an increase in the reticulocyte count. Due to the slow release of bioavailable iron serum ferritin peaks within days after an intravenous dose of iron(III) and slowly returns to baseline after weeks.

The iron(III) formulation contains iron in a strongly bound complex that enables a controlled and slow release of bioavailable iron to iron-binding proteins with little risk of free iron toxicity. After administration of a single dose of iron(III) of 100 to 1000 mg of iron in pharmacokinetic studies, the iron injected or infused was cleared from the plasma with a half-life that ranged from 1 to 4 days. Renal elimination of iron was negligible.

Following intravenous administration, iron isomaltoside 1000 is rapidly taken up by the cells in the reticuloendothelial system (RES), particularly in the liver and spleen from where iron is slowly released.

Circulating iron is removed from the plasma by cells of the reticuloendothelial system which split the complex into its components of iron and isomaltoside 1000. The iron is immediately bound to the available protein moieties to form hemosiderin or ferritin, the physiological storage forms of iron, or to a lesser extent, to the transport molecule transferrin. This iron, which is subject to physiological control, replenishes haemoglobin and depleted iron stores.

Iron is not easily eliminated from the body and accumulation can be toxic. Due to the size of the complex, iron(III) is not eliminated via the kidneys. Small quantities of iron are eliminated in urine and faeces.

Isomaltoside 1000 is either metabolised or excreted.

Iron complexes have been reported to be teratogenic and embryocidal in non-anaemic pregnant animals at high single doses above 125 mg iron/kg body weight. The highest recommended dose in clinical use is 20 mg iron/kg body weight.

In a fertility study with iron(III) in rats no effects on male reproductive performance and spermatogenic parameters were found at dose level tested.