Ferrum lek

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FERRUM LEC (FERRUMLEK®)

Composition:

Active substance: 1 tablet contains 100 mg of iron (III) in the form of a complex of iron (III) hydroxide with polymaltose;

Excipients: polyethylene glycol (macrogol 6000), aspartame (E 951), chocolate flavoring, talc, dextrins.

Pharmaceutical form. Chewable tablets.

Main physicochemical properties: brown-white tablets with speckles, round, flat, with bevelled edges.

Pharmaco-therapeutic group. Anti-anemic agents. Oral iron (III) preparations. ATC code B03AB05.

Pharmacological Properties.

Pharmacodynamics.

The drug contains iron in the form of iron (III) hydroxide polymaltose complex. This macromolecular complex is stable and does not release iron as free ions into the gastrointestinal tract. The structure of the drug resembles the natural iron compound—ferritin. Due to this similarity, iron (III) is absorbed from the intestine into the bloodstream via active absorption. Absorbed iron binds to ferritin and is stored in the body, primarily in the liver. Later, in the bone marrow, it is incorporated into hemoglobin. The iron preparation is presented as a polymaltose complex of Fe3+ hydroxide. Externally, the polynuclear Fe3+ hydroxide cores are surrounded by multiple non-covalently bound polymaltose molecules, forming a complex with a molecular weight of 50 kDa, which is so large that its diffusion through the intestinal mucosal membranes is approximately 40 times lower than that of Fe2+ hexahydrate. Iron contained in the iron (III) hydroxide polymaltose complex does not exhibit pro-oxidant properties typical of simple iron salts. Consequently, susceptibility to oxidation of very low-density lipoproteins and low-density lipoproteins is reduced.

Pharmacokinetics.

Studies using the dual-isotope method (55Fe and 59Fe) have shown that iron absorption, measured by erythrocyte hemoglobin levels, is inversely proportional to the administered dose of the drug (the higher the dose, the lower the absorption). There is a correlation between the degree of iron deficiency and the amount of iron absorbed (the greater the iron deficiency, the better the absorption). The most active absorption process occurs in the duodenum and small intestine. Unabsorbed iron is excreted in feces. Iron excretion occurring through desquamation of the gastrointestinal and skin epithelium, as well as through sweat, bile, and urine, amounts to only 1 mg per day. In women, iron loss during menstruation must also be considered.

Clinical characteristics.

Indications.

Treatment of iron deficiency without anaemia (latent iron deficiency) and iron deficiency anaemia (clinically evident iron deficiency).

Iron deficiency and its severity must be confirmed by appropriate laboratory tests.

Contraindications.

Known hypersensitivity or intolerance to the active substance or any component of the medicinal product; iron overload (e.g., haemochromatosis, haemosiderosis); disorders of iron excretion mechanisms (lead-induced anaemia, sideroachrestic anaemia, thalassaemia); anaemias not caused by iron deficiency (e.g., haemolytic anaemia, vitamin B12 deficiency-induced megaloblastic anaemia); oesophageal stricture and/or other obstructive gastrointestinal disorders; intestinal diverticulum, intestinal obstruction, regular blood transfusions; concomitant use of parenteral iron preparations.

Interaction with other medicinal products and other forms of interaction.

Studies in rats using tetracycline, aluminium hydroxide, acetylsalicylic acid, sulfasalazine, calcium carbonate, calcium acetate, calcium phosphate combined with vitamin D3, bromazepam, magnesium aspartate, D-penicillamine, methyldopa, paracetamol, and auranofin did not reveal any interaction with iron(III) hydroxide polymaltose complex.

In vitro studies showed no interaction between the medicinal product and food components such as phytic acid, oxalic acid, tannin, sodium alginate, choline and choline salts, vitamin A, vitamin D3, vitamin E, soybean oil, and soy flour. These results indicate that iron(III) hydroxide polymaltose complex can be administered during or immediately after meals.

Interaction between iron(III) hydroxide polymaltose complex and tetracycline or aluminium hydroxide was investigated in three clinical studies (crossover studies involving 22 patients each). No significant reduction in tetracycline absorption was observed. Tetracycline plasma concentrations did not fall below the level required for efficacy. Administration of aluminium hydroxide and tetracycline did not reduce iron absorption from iron(III) hydroxide polymaltose complex. Therefore, the medicinal product may be used concomitantly with tetracyclines, other phenolic compounds, and aluminium hydroxide.

Concomitant use of parenteral iron preparations and Ferum Lek is not recommended, as such use inhibits absorption of orally administered iron preparations. Parenteral iron preparations may be used when treatment with oral iron is not suitable.

Administration of the medicinal product does not affect the results of the haemoglobin-sensitive faecal occult blood test; therefore, there is no need to discontinue treatment during testing.

Special precautions for use.

Treatment of anemia should always be carried out under medical supervision. If there is no improvement in hematological parameters (an increase in hemoglobin levels by approximately 20–30 g/L within 3 weeks after starting treatment), the treatment regimen should be re-evaluated.

Caution should be exercised in patients receiving repeated blood transfusions, as red blood cells already contain iron stores, and administration of the drug may lead to iron overload.

If anemia is caused by infection or a malignant tumor, iron administered into the body accumulates in the reticuloendothelial system and is not utilized. Therefore, oral iron preparations may be administered only after successful treatment of the underlying disease, taking into account the benefit/risk ratio.

When prescribing the drug to patients with diabetes mellitus, it should be considered that 1 chewable tablet contains 0.04 bread units.

One tablet contains 1.5 mg of aspartame (a precursor of phenylalanine), which should be taken into account when prescribing the drug to patients with phenylketonuria.

Iron preparations should be used with caution in patients with the following conditions: leukemia, chronic liver or kidney diseases, inflammatory gastrointestinal disorders, peptic ulcer of the stomach or duodenum, intestinal diseases (enteritis, ulcerative colitis, Crohn's disease).

During administration of the iron polymaltose complex, dark stool color may occur; however, this is not of clinical significance.

Clinical data on the use of the drug in patients with hepatic or renal insufficiency are limited. A careful benefit/risk assessment should be performed for these patients before prescribing the medicinal product.

Use during pregnancy or breastfeeding.

Data on use during the first trimester of pregnancy do not indicate adverse effects on pregnancy or on the health of the fetus or newborn. Animal studies have not revealed any direct or indirect harmful effects on pregnancy, embryonic or fetal development. Nevertheless, the drug should be used with caution during pregnancy.

Human breast milk contains iron bound to lactoferrin. It is unknown how much iron from the iron(III) hydroxide polymaltose complex passes into breast milk. It is unlikely that administration of the drug will have adverse effects on a breastfed infant.

Use of the drug during pregnancy or breastfeeding is recommended only after consultation with a physician and careful evaluation of the benefit/risk ratio.

Ability to influence reaction rate while driving or operating machinery.

Appropriate studies have not been conducted. It is unlikely that the drug affects reaction speed while driving or operating complex machinery.

Dosage and Administration

The daily dose of the drug and duration of treatment depend on the degree of iron deficiency.

Treatment of iron deficiency without anemia. The recommended dose for children aged 12 years and older and adults is 1 tablet per day (100 mg of iron).

Treatment of iron deficiency anemia. The recommended dose for children aged 12 years and older and adults is 1–3 tablets per day (100–300 mg of iron).

The daily dose can be taken once daily or divided into several doses taken during or immediately after meals. Ferro-Lek, chewable tablets, may be chewed or swallowed whole.

The duration of treatment for clinically evident iron deficiency (iron deficiency anemia) is on average 3–5 months until hemoglobin levels normalize. After this, the drug should be continued at the appropriate dosage to treat latent iron deficiency for several additional weeks to replenish iron stores.

The duration of treatment for latent iron deficiency without anemia is 1–2 months.

Children.

The drug is indicated for children aged 12 years and older. For children under 12 years of age, Ferro-Lek syrup is recommended.

Overdose.

No signs of intoxication or excessive iron accumulation in the body have been observed with this drug due to the specific characteristics of controlled release and the low toxicity of the iron(III) hydroxide polymaltose complex (in mice and rats, LD50 > 2000 mg iron/kg body weight). There have been no reports of accidental overdose resulting in fatal outcomes.

Side effects

The frequency of adverse reactions is defined as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), frequency not known (cannot be calculated from available data). The most commonly reported adverse reaction is change in stool color (in 23% of patients), caused by excretion of iron. This is not of clinical significance.

Immune system: very rare – allergic reactions.

Nervous system: uncommon – headache.

Gastrointestinal tract: very common – change in stool color¹; common – diarrhea, nausea, dyspepsia, heartburn; uncommon – abdominal pain², vomiting³, constipation, discoloration of tooth enamel, gastritis.

Skin and subcutaneous tissue: uncommon – skin hypersensitivity reactions, e.g. exanthema, rash, urticaria, pruritus^5,6; frequency not known – anaphylactic reactions.

Musculoskeletal and connective tissue disorders: muscle spasms⁴, myalgia.

¹ According to meta-analysis results, reports of stool color change were rare, although this adverse reaction is common with iron-containing preparations.

² Including abdominal pain, dyspepsia, stomach discomfort, bloating.

³ Including vomiting, regurgitation.

⁴ Including muscle spasms, tremor.

⁵ Including skin eruptions, maculopapular rash, vesicular rash.

⁶ The reported incidence after marketing authorization is approximately <1/491 patients (95%).

Shelf life. 5 years.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging. 10 tablets per strip or blister; 3 (10 × 3) strips or blisters per cardboard box.

Prescription category. Prescription only.

Manufacturer.

Lek Pharmaceuticals d. d.

Manufacturer's address and place of business.

Verovškova 57, 1526 Ljubljana, Slovenia

or

Trimlin 2d, 9220 Lendava, Slovenia.