Polymaltose Complex Research Articles

Iron Polymaltose Versus Ferrous Gluconate in the Prevention of Iron Deficiency Anemia of Infancy

We prospectively compared the efficacy and safety of iron deficiency anemia prophylaxis with iron gluconate (IG) or iron polymaltose complex (IPC) in healthy infants attending a community pediatric center. Participants were randomly assigned to receive one of the test drugs from age 4 to 6 months to age 12 months. Parents/guardians were given extensive information on iron-rich diets and anemia prevention. Main outcome measures were blood levels of hemoglobin, hematocrit, mean corpuscular volume, red blood cell distribution width, and serum iron, ferritin, and transferrin, in addition to adverse effects. One hundred five children completed the study: 53 in the IG group and 52 in the IPC group Mean hemoglobin levels at study end were significantly higher in the IG group (12.04±0.09 g/dL vs. 11.68±0.11, P<0.014). A hemoglobin level <11 g/dL was detected in 3 infants of the IG group, and in 10 infants of the IPC group (P<0.04). Adverse effects (spitting, vomiting, diarrhea, constipation, discolored teeth) were significantly more common in the IG group (47% vs. 25%, P>0.025). In conclusion, both oral IG and IPC prevent iron deficiency anemia in infants. Iron gluconate seems to be more effective but less tolerable.

Is adequate and balanced nutrition during pregnancy more effective than iron and folic acid supplements?

Abstract To provide instruction for pregnant women regarding adequate and balanced nutrition and determine whether iron and folic acid supplementation is essential. The research was an experimental clinical intervention. The study was conducted between March 2004 and May 2005 with 80 pregnant volunteers. The study participants were in their 16th to 24th weeks of pregnancy; all participants were healthy, carried only one fetus, and successfully completed their pregnancy. All participants were instructed about adequate and balanced nutrition. Until the participants gave birth, 40 (Group 1) consumed an iron-rich diet that was equivalent to the inclusion of a supplement containing 100 mg Ferro III plus 0,35 mg folic acid; the other group (Group 2) was also instructed in proper nutrition and was given by a gynecologist 1 tablet (100 mg) Ferro III hydroxide polymaltose complex and iron pharmaceutical with 0,35 mg folic acid (Maltofer Fol). In both groups, before and after the instruction, consumption frequency was noted, and the levels of serum ferritin, serum iron, total iron-binding capacity, folic acid, and vitamin B12 in the blood were determined at monthly intervals. Between the two groups, no statistical difference was found with regard to age, number of pregnancies, weight before pregnancy, body mass index (BMI) before pregnancy, and weight of the newborn (p&gt;0,05). At the end of the study, the hemoglobin, hematocrit, and serum ferritin levels decreased considerably in both groups compared to the initial values (p&lt;0.01). No statistically significant difference in serum ferritin levels could be found between the two groups (p&gt;0,05). The comparison of Group I and Group II in terms of nutritional status (average energy and food consumption) in the pre-instruction and post-instruction periods revealed that intake of total protein, heme protein, dietary fiber, folic acid, carotene, vitamins A, B1, B2, B6, C, and B12, potassium, calcium, phosphorus, iron, and zinc was higher in Group I in the post-instruction period (p=0.000); no statistically significant change in nutritional status during pregnancy was observed in Group II. Conclusion: Medical diet programs with iron sources are examined in association with food consumption. Assessment of hematological results suggests that, during pregnancy, each patient should receive a specific dose, rather than a routine dose, of iron and folic acid.

Iron supplementation for preterm infants receiving restrictive red blood cell transfusions: reassessment of practice safety

To reassess iron supplementation practice safety in very low birth weight (VLBW) preterm infants receiving restrictive red blood cell transfusions during initial hospitalization. Iron status, including hemoglobin (Hb), serum iron, ferritin, and soluble transferrin receptor (sTfR) levels and reticulocyte count of transfused (n=236) and non-transfused (n=166) preterm infants at ≤24 h and 2, 4 and 8 weeks were recorded. As per protocol, a restrictive blood transfusion policy and supplementation of 5 mg kg(-1) per day of iron polymaltose complex from 4 weeks and 25 mg(-1) per day of vitamin E from 2 weeks were imposed for all infants. Normative reference cord-blood ferritin value of preterm infants was used for comparison. Vitamin E levels and incidence of morbidities associated with prematurity were recorded. At ≤24 h, the characteristics and iron status of both groups were similar. At 2, 4 and 8 weeks, the transfused group had significantly higher Hb, iron and ferritin levels; sTfR levels were lower at 4 and 8 weeks (all indices, P<0.05). At 8 weeks, the median ferritin levels of our transfused group were lower than that of normative reference cord-blood value (115 (50th percentile) vs 79 (43 to 107) μg l(-1), respectively). Vitamin E levels and the incidence of morbidities associated with prematurity of the transfused and non-transfused groups were not different (both indices, P>0.18). Adding iron supplementation to preterm infants receiving restrictive blood transfusions has shown to be a judicious and safe practice in terms of iron status for VLBW preterm infants.

Comparison of effect of daily versus weekly iron supplementation during pregnancy on lipid peroxidation

To compare the effect of daily versus weekly iron supplementation on lipid peroxidation, hemoglobin levels and maternal and perinatal outcome in non-anemic pregnant women. Of 109 women randomly allocated into three groups, 90 completed the study. Group I (n = 30) received daily iron folic acid; Group II (n = 30) received weekly iron folic acid; Group III (n = 30) received daily iron (III)-hydroxide polymaltose complex. Hemoglobin levels, hematological indices, thiobarbituric acid reactive substances (TBARS) and glutathione levels were measured at baseline (14-16 weeks) and at 30-34 weeks. Statistical analysis was done using the anova test. Group I had a highly significant increase in TBARS level (0.61 +/- 0.26 micromol/L, P = 0.000) compared to groups II and III in which the change in TBARS was not significant (0.02 +/- 0.06 and 0.007 +/- 0.06 micromol/L, respectively). There was an insignificant fall in glutathione levels in all groups. There was no significant difference in the mean period of gestation, pregnancy complications and neonatal outcome between the three groups. Among 22.2% of women who were non-compliant, Group I had significantly higher incidence of non-compliance (P = 0.016) and side-effects (P = 0.001). Final hemoglobin was higher in Group I than II (11.9 +/- 1.2, 11.3 +/- 0.9, respectively, P = 0.041). The TBARS level was not statistically different between preterm and term deliveries. Nine out of 11 patients who developed hypertension during pregnancy had preeclampsia. The final TBARS level was significantly higher in these women (P = 0.000). Daily supplementation with ferrous sulphate results in greater lipid peroxidation than weekly supplementation, the latter is comparable with daily iron (III)-hydroxide polymaltose complex. Lipid peroxidation levels are significantly higher in preeclampsia.

Vitamin E Levels during Early Iron Supplementation in Preterm Infants

On the basis of preliminary data, this larger bi-institutional continuation trial evaluating the efficacy and safety of early iron supplementation in preterm infants calls attention to the levels of vitamin E, a marker of antioxidant activity, during iron treatment. A total of 116 preterm infants were randomly assigned to receive at 2 or 4 weeks of age ( N = 62, N = 54, respectively) 5 mg/kg/d of nonionic iron polymaltose complex concomitantly with a daily dose of 25 IU vitamin E (as dl-alpha-tocopherol acetate) from 2 weeks of age. Vitamin E (alpha-tocopherol) levels, iron, ferritin, hemoglobin concentration, and reticulocyte count were recorded from 2 to 8 weeks of age. The morbidities of prematurity associated with free radicals formation were also documented. A gradual increase of alpha-tocopherol levels within physiological range (0.8 to 3.5 mg/dL) was found in the 2-week and 4-week groups during the study period with no difference among the groups ( P > 0.05 for all comparisons). At 8 weeks of age, iron and ferritin levels, hemoglobin concentration, and reticulocyte count were higher in the 2-week group. No correlation was observed between timing of both iron and vitamin E supplement and hemolysis or morbidities associated with prematurity. Thus, treatment of iron with vitamin E supplement at 2 weeks of age is, in our experience, an efficacious and safe treatment for improving anemia in preterm infants.

Comparative Study of Gastrointestinal Tract and Liver Toxicity of Ferrous Sulfate, Iron Amino Chelate and Iron Polymaltose Complex in Normal Rats

Iron deficiency is a common worldwide problem leading to several morbidities including anemia. Although oral iron is the first choice in iron deficiency therapy, it may produce gastrointestinal (GI) and liver disorders. The aim of our study was to evaluate: (1) acute toxicity (LD₅₀) in different oral iron compounds such as ferrous sulfate (FS), iron amino chelate (AC) and iron polymaltose complex (IPC) and (2) possible differences in early and late toxicity in the GI tract and liver between them. Methods: Hematological variables, liver enzymes, oxidative stress markers (thiobarbituric-acid-reactive substances, reduced glutathione, catalase, glutathione peroxidase, CuZn superoxide dysmutase) in intestinal mucosa and liver homogenates, and morphological parameters (gross anatomy, histology) were evaluated in non-anemic rats. Results: LD₅₀ was lower (p < 0.01) in FS versus iron AC and IPC. The liver enzymes were increased in the FS group (p < 0.05). The FS group presented gastric mucosal erosions and the iron AC group showed submucosal hemorrhages in the lower GI tract (colon and rectum) versus the IPC and control groups. In the small intestine, the villi/crypt ratio and goblet cells per villus were significantly (p < 0.01) reduced in the FS and iron AC groups versus IPC. The eosinophils per villus were increased (p < 0.01) in the FS and iron AC groups versus the IPC and control groups. Ferritin was elevated (p < 0.01) in the IPC group versus FS and iron AC in the small intestine and liver. The oxidative stress markers were all significantly (p < 0.01) altered in the FS and iron AC groups versus the IPC and control groups in the intestinal mucosa and liver. Conclusion: FS exhibited important acute toxicity as well as early and late GI tract and liver toxicity. Despite showing similar LD₅₀ as IPC, iron AC presented differences regarding early and late GI tract and liver toxicity versus IPC.

The Efficacy and Safety of Early Supplementation of Iron Polymaltose Complex in Preterm Infants

The purpose of this study was to examine the efficacy and safety of early nonionic iron supplementation in preterm infants. Infants with gestational age < or = 32 weeks who were fed enriched human milk were assigned concurrently to receive 5 mg/kg/d enteral iron polymaltose complex (IPC) at 2 or 4 weeks of age. The levels of hemoglobin, reticulocytes, serum iron, ferritin, and soluble transferrin receptor were recorded at 2, 4, and 8 weeks of age. The incidence of morbidities associated with prematurity and the need for red blood cell transfusions (RBCTs) were recorded. The 2-week group (n = 32) had a better iron status than the 4-week group (n = 36) at 4 weeks and at 8 weeks of age. The incidence of morbidities associated with prematurity was not different among the groups ( P = 0.26). RBCT was required in one infants of the 2-week group and in 10 infants in the 4-week group ( P = 0.045). The number needed to treat to prevent one RBCT was five. Supplementation of 5 mg/kg/d enteral IPC to preterm infants fed enriched human milk as early as 2 weeks of age was more beneficial to iron status than at 4 weeks of age, and was associated with decreased need for RBCTs and no increase in the incidence of morbidities associated with prematurity.

Characterization and evaluation of spray dried co-processed excipients and their application in solid dosage forms

Major challenge for tablet manufacture comes from the powder characteristics of the materials to be compressed. This in turn poses a challenge in achieving greater productivity and better quality product especially on the new generation high-speed machines. Advancement in directly compressible materials has come in the form of co-processed spray dried materials. The present work evaluates and characterizes two spray dried co-processed materials, one comprising of microcrystalline cellulose, colloidal silicon dioxide and cross povidone and the other composed of microcrystalline cellulose, colloidal silicon dioxide and sodium starch glycollate. Prototype tablet formulations were developed with these co-processed materials using actives such as diclofenac sodium, iron polymaltose complex and amoxycillin trihydrate. Their performance was compared vis-a-vis conventionally processed tablet formulations as well as with leading marketed brands. This study revealed that the co-processed materials have excellent flow properties, high compressibility, render low disintegration time to tablets and have better binding properties. These materials can be a good substitute for inert granules, which are normally used in tablet manufacturing.

Intravenous Versus Oral Iron for Treatment of Anemia in Pregnancy

The aim of this study was to compare the efficacy of intravenous iron to oral iron in the treatment of anemia in pregnancy. In this randomized open-label study, 90 women with hemoglobin levels between 8 and 10.5 g/dL and ferritin values less than 13 microg/L received either oral iron polymaltose complex (300 mg elemental iron per day) or intravenous iron sucrose. The iron sucrose dose was calculated from the following formula: weight before pregnancy (kg) x (110 g/L - actual hemoglobin [g/L]) x 0.24 + 500 mg. Treatment efficacy was assessed by measuring hemoglobin and ferritin on the 14th and 28th days and at delivery, and the hemoglobin on the first postpartum day. Adverse drug reactions, fetal weight, hospitalization time, and blood transfusions were also recorded. Hemoglobin values varied significantly with time between groups (interaction effect, P < .001). The change in hemoglobin from baseline was significantly higher in the intravenous group than the oral group at each measurement; the changes with respect to subsequent hemoglobin were significantly higher on the 14th (P = .004) and 28th (P = .031) days. Ferritin values were higher in patients receiving intravenous iron throughout pregnancy. No serious adverse drug reactions were observed. Fetal weight and hospitalization time were similar in the 2 groups. Blood transfusion was required for only one patient in the oral group. Intravenous iron treated iron-deficiency anemia of pregnancy and restored iron stores faster and more effectively than oral iron, with no serious adverse reactions.

Effects of ferrous sulphate and non‐ionic iron–polymaltose complex on markers of oxidative tissue damage in patients with inflammatory bowel disease

Iron deficiency is a common complication of inflammatory bowel disease. Oral iron therapy may reinforce intestinal tissue injury by catalyzing production of reactive oxygen species. To compare the effects of ferrous sulphate and non-ionic iron-polymaltose complex on markers of oxidative tissue damage and clinical disease activity in patients with inflammatory bowel disease. Forty-one patients with inflammatory bowel disease and iron deficiency were randomized to treatment with ferrous sulphate 100 mg twice a day or iron-polymaltose complex 200 mg once a day for 14 days. Following ferrous sulphate, plasma malondialdehyde increased (P = 0.02), while urine 8-isoprostaglandin F(2alpha) and plasma antioxidants did not change significantly. Iron-polymaltose complex did not change plasma malondialdehyde, urine 8-isoprostaglandin F(2alpha) or plasma antioxidants. Comparing the two treatments, changes in plasma malondialdehyde tended to differ (P = 0.08), while urine 8-isoprostaglandin F(2alpha) and plasma antioxidants did not differ. Neither ferrous sulphate nor iron-polymaltose complex altered clinical disease activity indices. Ferrous sulphate increased plasma malondialdehyde, a marker of lipid peroxidation. Comparing treatment with ferrous sulphate and iron-polymaltose complex, changes in plasma malondialdehyde tended to differ. Clinical disease activity was unchanged after both treatments.

Kinetics of two different iron formulations and their effect on diurnal variation of serum iron levels

Iron polymaltose complex (IPC) is a recently marketed preparation with questionable bioavailability. We compared the absorption kinetics of IPC with ferrous sulfate. We also studied the effect of oral iron on diurnal variation. The study was conducted in eight healthy, non-smoking, non-alcoholic volunteers after obtaining their written informed consent and after Institutional Ethical Committee approval. The study was conducted in three phases: during the first phase no drugs were given, whereas in the second and third phases, ferrous sulfate (66 mg elemental iron) and IPC (100 mg elemental iron) were given in a randomized, two-way, cross-over design, with a wash-out period of 1 week. The blood samples were collected, iron levels estimated and the pharmacokinetic parameters calculated. Circadian rhythm in iron levels was demonstrated by cosinor analysis with a mesor of 93.6 microg/dl, acrophase 10.40 h and amplitude of 26.4 microg/dl. Evening levels were higher as compared with morning levels. Drug treatment increased the mesor (115.7 microg/dl; p < 0.05), delayed the acrophase (11.30 h; p < 0.05) and increased the amplitude (38.5 microg/dl; p < 0.05). The bioavailability of ferrous sulfate was significantly greater as compared with IPC with greater Cmax and AUC (p < 0.05). A clear cut circadian rhythm in iron concentrations was demonstrated. Ferrous sulfate was shown to have significantly higher bioavailability as compared with IPC. Further studies having hemoglobin levels as an endpoint may be planned.

Experience with the Use of an Iron Polymaltose (Dextrin) Complex Given by Single Total Dose Infusion to Stable Chronic Haemodialysis Patients

Background: Many studies of anaemia in patients on chronic haemodialysis have noted a high prevalence of iron deficiency despite oral iron supplementation. Our study examined the effect of intravenous iron given as bolus replacement. As the majority of these patients were not receiving concurrent recombinant human erythropoietin (rhEPO) it allowed an analysis of the safety and efficacy of intravenous iron as a single agent. Methods: All patients with a haemoglobin level of less than 10 g/dl and considered iron deficient by the finding of a percentage transferrin saturation of less than 20% were given intravenous iron in the form of iron polymaltose (dextrin) by total dose infusion (TDI). The dose was calculated from tables supplied by the manufacturers. Patients with serum ferritin levels in excess of 225 ng/ml were excluded. Results: In our unit, 62 out of 80 (77%) patients were considered iron deficient and received IV iron. Ten (10%) were considered to be in iron balance and 8 (10%) had biochemistry suggesting iron overload. None of the patients receiving iron experienced any adverse reactions. At three months a rise in haemoglobin level of at least 1 g/dl was noted in 53% of patients. The response was less in the remainder, but only 2 showed no response. Conclusions: Low levels of iron deficiency are often unrecognized in chronic haemodialysis patients on conventional therapy including oral iron supplementation. In such patients, the use of total dose infusion of iron polymaltose (dextrin) is a safe and effective method of raising haemoglobin levels. Substantial improvements may be achieved without the concurrent use of rhEPO.

Oral supplementation with ferrous sulfate but not with non-ionic iron polymaltose complex increases the susceptibility of plasma lipoproteins to oxidation

Iron deficiency anemia is customarily treated by iron supplementation. However, iron can act as a catalyst of lipid peroxidation in vitro, and high intake of heme iron has been associated with an increased risk of myocardial infarction in some, but not in all epidemiologic studies. We carried out a 6-month trial of the effects of supplementation of men (n=48) with low iron stores with ferrous sulfate (180 mg of iron per day), iron polymaltose complex (200 mg of iron per day) or placebo. The in vitro susceptibility of very low and low density lipoproteins to oxidation increased in the ferrous sulfate group by 8.8% (P<0.05) compared to placebo and by 12.8% (P<0.05) compared to iron polymaltose complex. The produced amount of a lipid peroxidation product increased in the ferrous sulfate group by 13.8% (P<0.05) compared to the iron polymaltose complex group. This study suggests a role for ionic rapidly absorbed and distributed iron in oxidation susceptibility of lipoproteins in humans. Our findings have implications regarding the treatment of iron deficiency anemia. They indicate that a rapid correction of iron stores by supplementation with high dose ferrous sulfate, at least in combination with ascorbate, can have undesirable effects and suggest that if iron supplementation is necessary, non-ionic iron polymaltose products are preferable to ferrous sulfate.

Inflammatory siderosis of the nervous system in rats.

Large intravenous doses of a relatively nontoxic iron polymaltose complex were taken up by liver and spleen and did not enter the central nervous system (CNS) of normal rats. When the injections were given during development of the inflammatory lesions of experimental allergic encephalomyelitis (EAE), many iron-laden macrophages entered vessels, perivascular cuffs and neural parenchyma. Iron polymaltose injected before the EAE lesions started to develop, or during the healing phase, did not enter the lesions. This model of CNS siderosis may be useful for studies on long-term effects of iron and for neuroimaging by nuclear magnetic resonance.