CosmoFer Mechanism of Action

Pharmacology: Pharmacotherapeutic group: Iron parenteral preparation. ATC code: B03AC.
Pharmacodynamics: CosmoFer 50 mg/mL solution for injection and infusion contains iron as a stable iron(III)-hydroxide dextran complex, which is analogous to the physiological form of iron, ferritin (ferric hydroxide phosphate protein complex). The iron is available in a non-ionic water-soluble form. It has a very low toxicity and can be given in large doses. Serum ferritin peaks approximately 7 to 9 days after an intravenous dose of CosmoFer and slowly returns to baseline after about 3 weeks.
Examination of the bone marrow for iron stores may not be meaningful for prolonged periods following iron dextran therapy because residual iron dextran may remain in the reticuloendothelial cells.
Pharmacokinetics: Following the i.v. infusion the iron dextran is rapidly taken up by the cells in the reticuloendothelial system (RES), particularly in the liver and spleen from where iron is slowly released and bound to proteins. After administration an increased hematopoiesis can be observed for the next 6-8 weeks. The plasma half life is 5 hours for circulating iron and 20 hours for total iron (bound and circulating).
Circulating iron is removed from the plasma by cells of the reticuloendothelial system which split the complex into its components of iron and dextran. The iron is immediately bound to the available protein moieties to form hemosiderin or ferritin, the physiological forms of iron, or to a lesser extent, to 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 (165,000 Daltons) it is not eliminated via the kidneys. Small quantities of iron are eliminated in urine and faeces.
After intramuscular injection, iron dextran is absorbed from the injection site into the capillaries and the lymphatic system. The major portion of the intramuscularly administered iron dextran is absorbed within 72 hours; most of the remaining iron is absorbed during the ensuing 3 to 4 weeks.
Dextran is either metabolised or excreted.
Toxicology: Preclinical safety data: CosmoFer has been reported to be teratogenic and embryocidal in non-anaemic pregnant animals at high single doses above 125 mg/kg. The highest recommended dose in clinical use is 20 mg/kg. However, no detailed information is available from these studies.
In vitro and in vivo genotoxicity studies have showed mutagenic activity after the administration of high doses of iron-dextran complexes. However the significance of these results is not clear. Iron dextran was not mutagenic at sub-toxic dose levels. There are no other additional preclinical data of relevance to the prescriber than those already included in other sections of the package insert.