Folic acid

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FOLIC ACID (Folic acid)

Composition:

Active substance: 1 tablet contains 1 mg of folic acid;

Excipients: sugar, potato starch, calcium stearate.

Pharmaceutical form. Tablets.

Main physico-chemical properties: tablets of flat cylindrical shape with bevelled edges and a score line, pale yellow in colour.

Pharmacotherapeutic group. Antianaemic agents. Folic acid and its derivatives.

ATC code B03B B01.

Pharmacological properties.

Pharmacodynamics.

After administration, folic acid is reduced to tetrahydrofolic acid, which acts as a coenzyme involved in various metabolic processes. Folic acid is necessary for the normal maturation of megaloblasts and the formation of normoblasts. It stimulates erythropoiesis and participates in the synthesis of amino acids (including methionine, serine, glycine and histidine), nucleic acids, purines, and pyrimidines, as well as in choline metabolism.

Pharmacokinetics.

After oral administration, folic acid is well and completely absorbed from the gastrointestinal tract, primarily in the upper part of the duodenum. It is almost completely bound to plasma proteins. It undergoes activation in the liver under the action of the enzyme dihydrofolate reductase, converting into tetrahydrofolic acid. Maximum blood concentration is reached within 30–60 minutes.

Excretion occurs mainly via the kidneys in the form of metabolites; if the administered dose significantly exceeds the daily requirement for folic acid, the vitamin is excreted unchanged in the urine. Renal excretion occurs through glomerular filtration; 5 mg of orally administered folic acid is eliminated from the body within 5 hours. Folic acid is removed from the systemic circulation during hemodialysis.

Clinical characteristics.

Indications.

Macrocytic anemias, particularly megaloblastic anemias in pregnant women; for the treatment of sprue to normalize hematopoiesis, eliminate or reduce clinical manifestations of the disease. Anemias and leukopenias caused by ionizing radiation, chemicals, including drugs; anemias resulting from gastrectomy or intestinal resection; megaloblastic anemias caused by intestinal tuberculosis and chronic gastroenteritis (in these conditions, it is indicated even in the absence of anemia); pernicious anemias, pellagra. As an adjunctive agent in depression and anxiety disorder, and in the treatment of cervical dysplasia.

Contraindications.

Hypersensitivity to folic acid or to any component of the medicinal product, vitamin B12 deficiency, malignant neoplasms, malignant anemias, untreated cobalamin deficiency.

Interaction with other medicinal products and other forms of interaction.

In patients with folate deficiency, administration of folic acid may reduce plasma levels of phenobarbital, phenytoin, and primidone and may provoke epileptic seizures. Drugs that may cause folic acid deficiency include: antituberculosis agents, folic acid antagonists such as pyrimethamine, triamterene, trimethoprim.

Oral contraceptives, ethanol, sulfasalazine, cycloserine, glutethimide, and methotrexate may affect folate metabolism.

Folic acid enhances phenytoin metabolism. Cases of decreased or altered absorption may occur when cholestyramine and folic acid are used concomitantly. Therefore, the medicinal product should be administered 1 hour before or 4–6 hours after cholestyramine.

Absorption of folic acid is reduced when used concomitantly with analgesics, anticonvulsants, antacids, chloramphenicol, neomycin, polymyxins, antibiotics, sulfonamides, and cytostatics.

Acetylsalicylic acid may increase elimination of folic acid. Folates enhance the effectiveness of lithium. Nitrous oxide may cause acute folic acid deficiency.

Avoid concomitant use with fluorouracil. Antacid preparations containing aluminum or magnesium may reduce absorption of folic acid; therefore, patients should be advised to take antacids 2 hours after administration of folic acid. Folic acid may reduce intestinal absorption of zinc.

Do not use together with mineral acids, alkaline substances, or reducing agents, as inactivation of folic acid occurs.

Special precautions for use.

The medicinal product should be administered with caution to patients with anemias of unknown etiology, since folic acid may interfere with the diagnosis of pernicious anemia by improving hematological manifestations of the disease, while allowing neurological complications to progress.

Prolonged use of folic acid (especially in high doses) is not recommended due to the possible decrease in blood concentration of cyanocobalamin (vitamin B12).

Systematic monitoring of blood parameters is required during treatment with folic acid.

The medicinal product contains sugar, which should be taken into account in patients with diabetes mellitus and in patients with glucose-galactose malabsorption syndrome.

Folic acid should be used in combination with other medicinal products: in pernicious anemia – only in combination with cyanocobalamin, since folic acid, while stimulating hematopoiesis, does not prevent the development of neurological complications (e.g., funicular myelosis); in sprue – in combination with ascorbic acid, cyanocobalamin, and with concomitant hemotherapy.

In elderly patients, a cobalamin absorption test should be performed prior to initiating long-term therapy.

This medicinal product is not intended for healthy pregnant women, for whom the lowest doses may be recommended, but should be prescribed to pregnant women with folic acid deficiency or to women at risk of recurrence of neural tube defects.

Use during pregnancy or breastfeeding.

For therapeutic purposes, the medicinal product may be used as directed by a physician, in the doses and duration specified in the instructions.

Deficiency of folic acid or disturbances in folic acid metabolism are associated with the occurrence of congenital defects and certain neural tube defects. Interference with folic acid metabolism or folic acid deficiency due to the action of certain medicinal products, such as anticonvulsants or antineoplastic agents, during early pregnancy may lead to congenital anomalies.

Lack of the vitamin or its metabolites may also contribute to spontaneous abortion and intrauterine growth retardation.

Ability to influence reaction rate when driving or operating machinery. There is no data on a negative effect of folic acid on the ability to drive or operate machinery.

Dosage and Administration.

Folic acid should be taken orally after meals.

The dosage and duration of treatment are determined by a physician depending on the nature and course of the disease.

For therapeutic purposes, the medicinal product is prescribed to adults at a dose of 1–2 mg (1–2 tablets) 1–3 times daily. Maximum daily dose – 5 mg (5 tablets).

For children aged 3 years and older, depending on the child's age and the nature of the disease, the medicinal product is prescribed at a dose of 1 mg (1 tablet) 1–2 times daily. Maximum daily dose – 2 mg (2 tablets).

The usual treatment course lasts 20–30 days.

In cases of macrocytic anemia, the medicinal product is prescribed to adults at a dose of 5 mg 2–3 times daily for 10–15 days.

Pregnant women with reduced hemoglobin levels in the first trimester should be administered folic acid at a dose of 4 mg daily in combination with iron preparations for 3 months. Afterward, the dose of folic acid should be reduced to 4 mg once weekly.

Children. The use of this medicinal product is contraindicated in children under 3 years of age.

Overdose.

Overdose of folic acid may mask vitamin B12 deficiency.

Prolonged and significant exceeding of recommended doses may lead to dangerous accumulation of folacin crystals, resulting in body intoxication and increased adverse effects.

Treatment. Discontinuation of the medicinal product and symptomatic therapy.

Adverse reactions.

The medicinal product is well tolerated.

Gastrointestinal disorders: nausea, vomiting, bloating, flatulence, bitter taste, anorexia.

Immune system disorders: allergic reactions, including skin rash, erythema, urticaria, pruritus, and respiratory disturbances due to bronchospasm, arterial hypotension, anaphylactic reactions.

Central nervous system disorders: malaise, sleep disturbances, convulsions.

Renal and urinary disorders: hypertrophy of epithelial cells in renal tubules and impairment of their function.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in blisters.

10 tablets in a blister; 3 blisters in a carton.

Availability. Over-the-counter.

Manufacturer. JSC "KYIV VITAMIN PLANT".

Manufacturer's address and place of business.

38, Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua.