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Pharmacotherapeutical group: iron preparations, iron in combination with folic acid. ATC Code: B03AD04.
Pharmacology: Properties: In iron(III)-hydroxide polymaltose complex, the polynuclear iron(III)-hydroxide core is superficially surrounded by a number of non-covalently bound polymaltose molecules resulting in an overall average molecular weight of approximately 50 kDa. The polynuclear core of IPC has a structure similar to that of the physiological iron storage protein, ferritin. IPC is a stable complex and does not release large amounts of iron under physiological conditions. Because of its size, the extent of diffusion of IPC through the membrane of the mucosa is about 40 times less than that of the hexaquo-iron(II) complex. Iron from IPC is taken up in the gut via an active mechanism.
Folic acid (folate) is a member of the Vitamin B group. It is a tetrahydrofolate precursor, a coenzyme involved in various metabolic processes including the biosynthesis of nucleic acid purines and thymidylates. Folic acid is required for nucleoprotein synthesis and maintenance of normal erythropoiesis.
Pharmacodynamics: The iron absorbed is bound to transferrin and is used for Hb synthesis in the bone marrow or stored primarily in the liver bound to ferritin.
Clinical Efficacy: During pregnancy, there is an increased requirement for iron which is approximately 0.8 mg/day in the first trimester and up to 6 mg/day during the third trimester of pregnancy. In addition, there is an increased requirement for folic acid, particularly during pregnancy. Low folic acid levels can lead to signs of deficiency in both mothers (anaemia, peripheral neuropathies) and the foetus (congenital neural tube defects).
Clinical studies have been carried out in pregnant women to investigate the safety and efficacy of the treatment of iron deficiency with or without anaemia, as well as to prevent an iron and folic acid deficiency with IPC treatment in combination with folic acid (Maltofer Fol). Changes in haematological parameters were compared during treatment with Maltofer Fol chewable tablets at a dose of 100 mg-300 mg iron/day in conjunction with 0.35 mg folic acid/day in comparison to iron(II) sulphate standard preparations with and without folic acid. A study investigated the efficacy of IPC with the addition of a folic acid supplement compared to intravenous iron administration, and another study examined the efficacy and tolerability of Maltofer Fol compared to a diet high in iron. In total, approximately 700 pregnant women with normal and decreased iron were included, and more than 400 of these patients received Maltofer Fol.
Treatment of pregnant women with Maltofer Fol showed similar improvements in haematological parameters compared to results with Maltofer in non-pregnant patients with at the same time a good tolerability. An improvement in the haemoglobin values to an average of 0.72 to 2.2 g/dL (p<0.05) as compared to the start of treatment was observed in the clinical studies following treatment with Maltofer Fol lasting between 30 days and 2.5 months. In addition, improvements were measured in serum ferritin (+5.74 mcg/L) and in red blood cell ferritin levels (on average +6.3 mcg/g or 5.74 mcg/g after treatment lasting 30 days or 2.5 months compared to the baseline).
An open study investigated the efficacy of Maltofer Fol (200 mg IPC/day for 10 days and 100 mg/day for 20 days) with supplemental vitamin B12 in pregnant women with iron deficiency anaemia. There was a significant increase in haemoglobin values as well as in the haematocrit, the number of erythrocytes and folic acid values. (p<0.01).
An open study with 43 young adults with varying degrees of iron deficiency anaemia between the ages of 14.5 and 17 years investigated the efficacy of Maltofer Fol on haemoglobin levels. Changes in the Hb values after 48 to 49 days of treatment compared to the baseline were 10.44 ±0.08 g/dL, 11.64 ±0.07 g/dL and 13.41 ±0.13 g/dL with mild, moderate or severe anaemia, and after 75 to 76 days of treatment 13.32 ±0.11 g/dL and 12.64 ±0.07 g/dL (moderate and severe anaemia).
Pharmacokinetics: Absorption: Studies with radio-labelled IPC show a good correlation between iron absorption and build-up of iron in haemoglobin. The relative absorption of iron correlates with the degree of iron deficiency (i.e. the greater the iron deficiency, the higher the iron absorption). In contrast to iron(II) salts, it was determined that food had no negative effect on the bioavailability of iron from Maltofer: significantly increased bioavailability of iron with concomitant ingestion of food was demonstrated in a clinical study, while three other studies showed a positive trend but no clinically significant effects. Around 80% of folic acid is absorbed in the small intestine, with maximum absorption occurring after 30-60 minutes.
Elimination: Iron that is not absorbed is eliminated in the faeces. Folic acid is mainly excreted in the urine.
Toxicology: Preclinical data: Non-clinical data obtained for IPC does not reveal any special hazards for humans based on conventional studies of individual dose toxicity and repeated dose toxicity, genotoxicity or reproduction and development toxicity.
The LD50 of IPC, which was determined in animal trials with mice and rats, was higher than an orally administered dose of 2‚000 mg of iron per kg of body weight.
