Instructions for use Maltofer Fol chewable tablets blister pack No. 30
Composition
active ingredient:
1 tablet contains 357 mg of iron (III) hydroxide polymaltozate, which is equivalent to 100 mg of iron, folic acid 0.35 mg;
excipients: microcrystalline cellulose, cocoa powder, sodium cyclamate, polyethylene glycol 6000, talc, vanillin, dextrates, chocolate flavoring.
Dosage form
Chewable tablets.
Main physicochemical properties: brown tablets with white inclusions and a score.
Pharmacotherapeutic group
Antianemic agent. Complex preparations containing iron and folic acid.
ATX code B0ZA D04.
Pharmacological properties
Pharmacodynamics.
The surface of the polynuclear iron(III) hydroxide base in the iron hydroxide polymaltose complex is surrounded by non-covalently bound polymaltose molecules, which results in an average total molecular weight of about 50 kDa. The structure of the polynuclear iron(III) hydroxide base in the iron–polymaltose complex is similar to that of ferritin, a physiological protein depot of iron. The iron hydroxide polymaltose complex is stable and does not release iron in large quantities under normal physiological conditions. Due to its size, the diffusion of the iron hydroxide polymaltose complex across the mucosa is approximately 40 times less than the diffusion of most water-soluble iron(II) salts contained in aqueous solutions as the hexaaqua-iron(II) complex. Iron from the polymaltose complex is absorbed in the intestine by active mechanisms. Folic acid (folate) is a B vitamin. It is a precursor of tetrahydrofolate, a coenzyme involved in various metabolic processes, including the biosynthesis of nucleic acids, purines, and thymidylates. Folic acid is necessary for the synthesis of nucleoproteins and the maintenance of normal erythropoiesis. Absorbed iron binds to transferrin and is used for hemoglobin synthesis in the bone marrow or is deposited mainly in the liver in a ferritin-bound form.
Clinical efficacy.
During pregnancy, the need for iron increases to approximately 0.8 mg/day during the first trimester and to 6 mg/day during the third trimester. In addition, the need for folic acid increases during pregnancy. Low folic acid levels can manifest as signs of deficiency in both the mother (anemia, peripheral neuropathy) and the fetus (neural tube defects).
Clinical studies were conducted in pregnant women to assess the safety and efficacy of iron deficiency with or without anemia and the prevention of iron and folic acid deficiency with polymaltose ferric hydroxide complex in combination with folic acid (Maltofer® Fol). Changes in hematological parameters were compared during treatment with Maltofer® Fol chewable tablets at a dose of 100–300 mg iron per day together with 0.35 mg folic acid per day compared with standard ferrous sulfate preparations with and without folic acid. One study evaluated the efficacy of polymaltose ferric hydroxide complex with folic acid compared with intravenous iron, and another study examined the efficacy and tolerability of Maltofer® Fol compared with a high-iron diet. The study included approximately 700 pregnant women with normal and low iron levels, more than 400 of whom received Maltofer® Fol.
Treatment of pregnant women with Maltofer® Fol demonstrated improvements in hematological parameters similar to those seen in non-pregnant patients with Maltofer®, and was well tolerated. In clinical trials, an increase in hemoglobin was observed on average by 0.72–2.2 g/dl (p < 0.05) compared to baseline with Maltofer® Fol, which was maintained for a period of 30 days to 2.5 months. In addition, improvements were observed in serum ferritin (+5.74 μg/l) and erythrocyte ferritin (on average +6.3 μg/g or 5.74 μg/g after 30 days to 2.5 months of treatment compared to baseline).
An open study evaluated the efficacy of Maltofer® Fol (200 mg of polymaltose iron hydroxide complex per day for 10 days and 100 mg/day for 20 days) in combination with vitamin B12 in the treatment of pregnant women with iron deficiency anemia. A significant increase in hemoglobin and hematocrit, erythrocyte count, and folic acid levels was observed (p < 0.01).
In an open-label study involving 43 subjects with iron deficiency anemia of varying severity, aged 14.5 to 17 years, the effect of Maltofer® Fol on hemoglobin levels was evaluated. The change in hemoglobin levels after 48–49 days of therapy compared to baseline was 10.44 ± 0.08 g/dl, 11.64 ± 0.07 g/dl and 13.41 ± 0.13 g/dl in patients with mild, moderate and severe anemia, respectively, and after 75–76 days of treatment – 13.32 ± 0.11 g/dl and 12.64 ± 0.07 g/dl (moderate and severe anemia, respectively).
A study with radiolabeled polymaltose ferric hydroxide complex showed a good correlation between iron absorption and iron accumulation in hemoglobin. There is a correlation between the degree of iron deficiency and the amount of iron absorbed (the greater the iron deficiency, the higher the absorption). It was found that food, unlike iron (II) salts, does not negatively affect the bioavailability of iron from Maltofer®: a clinical study demonstrated that the bioavailability of iron significantly increased when taken with food, while three other studies demonstrated only a positive trend, and not a significant clinical effect.
About 80% of folic acid is absorbed in the small intestine, with peak absorption occurring within 30–60 minutes.
Breeding.
Unabsorbed iron is excreted in the feces. Folic acid is excreted mainly in the urine.
Indication
Treatment and prevention of iron deficiency without anemia and iron deficiency anemia in conditions with increased need for folic acid during pregnancy or breastfeeding.
Iron deficiency and its severity must be confirmed by appropriate laboratory tests.
Contraindication
Hypersensitivity or intolerance to the active substance or any component of the drug;
excessive iron content in the body (for example, hemochromatosis, hemosiderosis);
disorder of iron excretion mechanisms (lead anemia, sideroachrestic anemia, thalassemia);
anemias not caused by iron deficiency (e.g., hemolytic anemia, megaloblastic anemia caused by vitamin B12 deficiency).
Interaction with other medicinal products and other types of interactions
Preclinical studies in rats using tetracycline, aluminum hydroxide, acetylsalicylic acid, sulfasalazine, calcium carbonate, calcium acetate, calcium phosphate in combination with vitamin D3, bromazepam, magnesium aspartate, D-penicillamine, methyldopa, paracetamol, and auranofin did not reveal any interactions with iron (III) hydroxide polymaltose complex.
In vitro studies have shown no interaction of iron(III) hydroxide polymaltose complex with food components such as phytic acid, oxalic acid, tannin, sodium alginate, choline and choline salts, vitamin A, vitamin D3 and vitamin E, soybean oil and soybean flour. The results of the study indicate that iron(III) hydroxide polymaltose complex can be taken with or immediately after meals.
The interaction of polymaltose iron(III) hydroxide complex with tetracycline or aluminum hydroxide was investigated in three clinical studies (cross-over studies involving 22 patients each). No significant reduction in tetracycline absorption was observed. The plasma concentration of tetracycline did not fall below the level required for bacteriostatic action. The use of aluminum hydroxide and tetracycline did not reduce the absorption of iron from polymaltose iron(III) hydroxide complex. Therefore, polymaltose iron(III) hydroxide complex can be used simultaneously with tetracyclines, other phenolic compounds and aluminum hydroxide.
The use of the drug does not affect the results of the test for detecting occult blood (sensitive to hemoglobin), so there is no need to stop treatment.
The concomitant use of parenteral iron preparations and Maltofer® Fol is not recommended, as this will inhibit the absorption of oral iron preparations. Parenteral iron preparations should only be used when treatment with oral preparations is not appropriate.
Folic acid may increase the metabolism of phenytoin, leading to decreased serum phenytoin concentrations, especially in patients with folic acid deficiency. Some patients may experience an increase in the frequency of epileptic seizures. Patients taking phenytoin or other anticonvulsants/anticonvulsants should consult a physician before using products containing folic acid.
It has been reported that concomitant administration of chloramphenicol and folic acid in folate-deficient patients may result in antagonism of the hematopoietic response to folic acid. Although the significance and mechanism of this interaction are unknown, the hematopoietic response to folic acid should be carefully monitored in patients receiving both drugs concurrently.
Application features
Treatment of anemia should always be carried out under the supervision of a physician. In the event that there is no improvement in hematological parameters (an increase in hemoglobin level of approximately 20–30 g/l 3 weeks after the start of treatment), the treatment regimen should be reviewed.
Maltofer® Fol contains folic acid, which may mask vitamin B12 deficiency. Potential vitamin B12 deficiency should be excluded in patients with anemia before starting treatment due to the risk of irreversible neurological disorders (see section "Contraindications").
Caution should be exercised in patients receiving repeated blood transfusions, as red blood cells already have a store of iron, and taking the drug may cause iron overload.
Infections and tumors can cause anemia. Oral iron supplements may be used after the underlying condition has been treated and the benefit/risk ratio has been considered.
When prescribing the drug to patients with diabetes, it is necessary to take into account that 1 tablet contains 0.03 bread units.
Iron preparations should be used with caution in patients with the following diseases: leukemia, chronic liver and kidney diseases, inflammatory diseases of the gastrointestinal tract, gastric and duodenal ulcers, intestinal diseases (enteritis, ulcerative colitis, Crohn's disease).
This medicine contains 10 mg sodium per tablet. This amount is equivalent to 0.5% of the WHO recommended maximum daily intake of sodium for adults, which is 2 g.
Use during pregnancy or breastfeeding
Clinical data on the use of the drug during pregnancy did not reveal any undesirable effects on pregnant women, as well as on the health of the fetus or newborn child. Data from epidemiological studies are not available. Animal studies did not reveal reproductive toxicity.
However, the drug should be used with caution during pregnancy.
Human breast milk contains iron and folic acid bound to lactoferrin. It is not known how much iron from iron(III) hydroxide polymaltose complex passes into breast milk. The use of Maltofer® Fol during pregnancy or breastfeeding is recommended only after consultation with a doctor.
Ability to influence reaction speed when driving vehicles or other mechanisms
No relevant studies have been conducted. It is unlikely that Maltofer® Fol affects the speed of reactions when driving or operating complex mechanisms.
Method of administration and doses
Treatment of iron deficiency anemia with increased folic acid requirement:
1 chewable tablet 2–3 times a day.
After normalization of hemoglobin levels: 1 chewable tablet per day at least until the end of pregnancy to restore iron stores.
Treatment and prevention of iron deficiency without anemia with increased folic acid requirement: 1 chewable tablet per day.
The daily dose of the drug can be divided into several doses or taken at once. Maltofer® Fol, chewable tablets, should be taken during or immediately after a meal, they can be chewed or swallowed whole.
Children: There are currently no data on the use of the drug in children.
Overdose
In case of overdose, intoxication or iron accumulation is unlikely due to the low toxicity of iron(III) hydroxide polymaltose complex (for mice and rats, the dose causing death in 50% of animals (LD50) is > 2000 mg iron/kg body weight), saturation of iron absorption is expected. No cases of unintentional overdose with fatal consequences have been reported.
There are reports that an excessive dose of folic acid can cause changes in the central nervous system (changes in mental status, changes in sleep patterns, irritability and hyperactivity), nausea, bloating, and flatulence.
Side effects
Adverse reactions are classified according to the following frequency: very common (> 1/10), common (< 1/10, ≥ 1/100), uncommon (< 1/100, ≥ 1/1000), rare (< 1/1000).
The safety profile and tolerability of Maltofer® were assessed based on a meta-analysis of data from 24 publications and clinical trial reports involving 1473 patients taking the drug. The most significant adverse drug reactions reported in these trials concerned four system organ classes (see below).
Faecal discoloration is a well-known adverse reaction to oral iron supplements, but this phenomenon is of no clinical significance and is often underreported. Other common adverse events were gastrointestinal disturbances (nausea, constipation, diarrhoea and abdominal pain).
From the immune system.
Very rare: allergic reactions.
From the digestive tract.
Very common: change in stool color*.
Common: diarrhea, nausea, abdominal pain (including abdominal pain, dyspepsia, epigastric discomfort, abdominal bloating), constipation.
Uncommon: vomiting (including retching, eructation), tooth enamel discolouration, gastritis.
On the skin and subcutaneous tissue.
Uncommon: pruritus, rash (including rash, macular rash, bullous rash**, urticaria**, erythema**).
From the nervous system.
Uncommon: headache.
Musculoskeletal and connective tissue disorders
Rare: muscle spasms (including involuntary muscle contractions, tremor), myalgia.
*The incidence of stool discoloration in the meta-analysis is lower, although it is a well-known adverse event with oral iron supplements. Therefore, stool discoloration was classified as a very common adverse event.
**Information on these events was obtained from spontaneous post-marketing reports; the frequency is estimated to be < 1/491 (upper limit of the 95% confidence interval).
Expiration date
5 years.
Storage conditions
Store in a place protected from light at a temperature not exceeding 25 ° C. Keep out of the reach of children!
Packaging
10 tablets in a blister; 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Vifor (International) Inc., Switzerland.
Location of the manufacturer and its business address.
Rechenstrasse 37, 9014 St. Gallen, Switzerland/ Rechenstrasse 37, 9014 St. Gallen, Switzerland.
