Folic acid

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FOLIC ACID

Composition:

Active substance: folic acid;

1 tablet contains 1 mg of folic acid;

Excipients: glucose monohydrate, stearic acid.

Pharmaceutical form. Tablets.

Main physicochemical properties: tablets of round shape with flat surface and bevelled edges, light yellow in colour. Non-uniformity of colour and minor specks are permissible.

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

ATC code B03B B01.

Pharmacological Properties

Pharmacodynamics

Folic acid belongs to the B vitamin group and is synthesized in the human body by intestinal microflora. After administration, folic acid is reduced to tetrahydrofolic acid, which acts as a coenzyme involved in various metabolic processes. It is necessary for the normal development of other blood cells, including the formation and maturation of megaloblasts and the production of normoblasts. In combination with vitamin B12 (cyanocobalamin), it stimulates hematopoiesis, partially erythropoiesis. Folic acid participates in the synthesis of amino acids (including methionine, serine, glycine, and histidine), nucleic acids, purines, and pyrimidines, and is involved in choline metabolism.

During pregnancy, folic acid protects the organism from the effects of teratogenic factors.

Folic acid deficiency leads to megaloblastic hematopoiesis; in pregnant women, this may result in fetal congenital abnormalities (neural tube defects, hydrocephalus, etc.). The most significant consequence of folic acid deficiency is reduced capacity for tissue repair and regeneration.

Pharmacokinetics

After oral administration, folic acid is well and completely absorbed from the gastrointestinal tract, primarily in the upper segment of the duodenum and the proximal part of the small intestine. It is almost entirely bound to plasma proteins. Approximately 87% of circulating folates are located within erythrocytes and 10–13% in blood serum. From the blood, folates enter the liver, where they are activated by the enzyme dihydrofolate reductase, converting into tetrahydrofolic acid. Maximum blood concentration is reached within 30–60 minutes. Elimination occurs primarily via the kidneys in the form of metabolites. If the administered dose significantly exceeds the daily requirement for folic acid, the kidneys begin to excrete the vitamin unchanged. Renal elimination occurs via 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 and eliminate or reduce clinical manifestations of the disease. Anemias and leukopenias caused by ionizing radiation, chemicals, including drugs; anemias occurring after gastrectomy or intestinal resection, megaloblastic anemias due to intestinal tuberculosis and chronic gastroenteritis (indicated also without anemia development), pernicious anemias, pellagra.

Folic acid deficiency associated with unbalanced or inadequate nutrition.

As an adjunctive agent in depression and anxiety disorders; in the treatment of cervical dysplasia.

Contraindications.

Hypersensitivity to folic acid or to any component of the drug, 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.

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

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

The following drugs may cause folic acid deficiency: antituberculosis agents, folic acid antagonists such as pyrimethamine, triamterene, trimethoprim.

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

Folic acid may reduce intestinal zinc absorption.

Folic acid must not be used concomitantly with mineral acids, alkalis, or reducing agents, as inactivation of folic acid may occur.

Avoid simultaneous combination with fluorouracil. Antacid preparations containing aluminum or magnesium may reduce folic acid absorption; therefore, patients should be advised to take antacids at least 2 hours after folic acid administration.

Folic acid enhances phenytoin metabolism. Decreased or altered absorption may occur when cholestyramine is used concomitantly with folic acid. Therefore, the drug should be administered at least 1 hour before or 4–6 hours after cholestyramine.

Special precautions for use.

Administer the drug with caution in patients with anemias of unknown etiology, as folic acid may interfere with the diagnosis of pernicious anemia by improving hematological manifestations of the disease, while allowing neurological complications to progress.

This medicinal product is not intended for use in healthy pregnant women. The lowest possible doses may be recommended; however, it should be prescribed to pregnant women with folic acid deficiency or to women at risk of recurrence of neural tube defects.

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

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

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

The product contains glucose, 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 and cyanocobalamin, along with hemotherapy.

Use during pregnancy or breastfeeding.

Folic acid deficiency or impaired folic acid metabolism is associated with the occurrence of congenital defects and certain neural tube defects. Interference with folic acid metabolism or folic acid deficiency due to certain medicinal products (e.g., anticonvulsants, antineoplastic agents) during early pregnancy may lead to congenital abnormalities. Vitamin deficiency or lack of its metabolites may also contribute to spontaneous abortion and intrauterine growth retardation.

For therapeutic purposes, the drug may be used as prescribed by a physician, in doses and duration as specified in the instructions.

Ability to influence reaction rate when driving or operating machinery.

There are no data indicating 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 the physician depending on the nature and course of the disease.

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

For prevention of folic acid deficiency associated with unbalanced or inadequate nutrition – 1–5 mg (1–5 tablets) per day. The treatment course lasts 20–30 days.

One month after completion of the course, repetition of treatment is recommended.

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

The usual treatment course lasts 20–30 days.

In cases of macrocytic anemia, the drug 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. After this period, the dose of folic acid should be reduced to 4 mg once weekly.

Children.

The use of the drug is contraindicated in children under 3 years of age.

Overdose.

Symptoms: folic acid overdose 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 drug, symptomatic therapy.

Adverse reactions.

The drug is well tolerated.

• Gastrointestinal tract: rarely – nausea, vomiting, bloating, flatulence, bitter taste; very rarely – anorexia;
• Immune system: rarely – allergic reactions, including skin rash, erythema, urticaria, pruritus, and respiratory disorders due to bronchospasm, arterial hypotension, anaphylactic reactions;
• Central nervous system: fever, sleep disturbances, seizures;
• Urinary system: 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 a blister pack. 3 or 5 blisters per carton.

25 tablets in a blister pack. 2 blisters per carton.

Supply classification. Over-the-counter.

Manufacturer.

JSC "VITAMINS".

Manufacturer's name and address of manufacturing site.

31 Uspenska Street, Uman, Cherkasy region, 20300, Ukraine.

Marketing Authorization Holder.

JSC "VITAMINS".

Address of the Marketing Authorization Holder and/or its representative.

31 Uspenska Street, Uman, Cherkasy region, 20300, Ukraine.