Folic acid

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FOLIC ACID (FOLIC ACID)

Composition:

Active substance: folic acid;

1 tablet contains 5 mg of folic acid;

Excipients: glucose monohydrate, stearic acid.

Pharmaceutical form. Tablets.

Main physical and chemical properties: yellow to dark yellow, round-shaped tablets with a flat surface and bevelled edges. Non-uniformity of color and minor specks are permissible.

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

ATC code B03B B01.

Pharmacological properties.

Pharmacodynamics.

After administration of the medicinal product, folic acid is reduced to tetrahydrofolate, a coenzyme involved in various metabolic processes. It is necessary for the normal maturation of megaloblasts and formation of normoblasts. It stimulates erythropoiesis, participates in the synthesis of amino acids (including methionine, serine, glycine, and histidine), nucleic acids, purines, and pyrimidines, and is involved in choline metabolism. It provides protection against the effects of teratogenic factors. In addition, it promotes normal maturation and functioning of the placenta.

Folic acid plays an important role in the maturation process of spermatozoa and can be used for the treatment of male infertility.

Folic acid deficiency leads to megaloblastic hematopoiesis; in pregnant women, this may cause congenital malformations in the fetus (neural tube defects, hydrocephalus, etc.). The most significant consequence of folic acid deficiency is reduced capacity for tissue repair.

Pharmacokinetics.

Folic acid is well absorbed from the gastrointestinal tract, primarily from the duodenum and small intestine. It is evenly distributed throughout all tissues and selectively concentrates in cerebrospinal fluid. The highest plasma concentration is reached within 30 to 60 minutes after oral administration.

It is metabolized in plasma and liver to 5-methyltetrahydrofolate, the active compound, which binds to glutamic acid to form a coenzyme. Approximately 50% of the total folic acid stores are stored in the liver. About 70% is bound to plasma proteins. It is excreted in urine via glomerular filtration. After administration of a 5 mg dose, folic acid is excreted in urine within 5 hours.

Clinical characteristics.

Indications

For the treatment and prevention of anemias associated with folic acid deficiency:

• macrocytic anemia;
• anemia and leukopenia caused by drugs and ionizing radiation;
• megaloblastic anemia, post-resection anemia;
• anemias in inflammatory bowel diseases (Crohn's disease, non-specific ulcerative colitis), malabsorption syndrome (gluten enteropathy or celiac disease), tropical sprue.

For the prevention of fetal congenital malformations: neural tube defects (hydrocephalus, encephalocele, "cleft palate", "harelip") — in women at risk who are planning pregnancy.

Folic acid deficiency associated with unbalanced or inadequate diet.

For the treatment of male infertility due to reduced spermatogenesis (oligospermia).

Contraindications

• Hypersensitivity to folic acid or to any of the excipients;
• malignant neoplasms, malignant anemias, untreated cobalamin deficiency;
• Addisonian pernicious anemia or other vitamin B12 deficiency states — since isolated use of folic acid in such patients may promote the development of subacute combined degeneration of the spinal cord;
• prolonged therapy with folic acid without treatment of cobalamin deficiency. This may be untreated pernicious anemia or another cause of cobalamin deficiency, including strict vegetarianism.

Interaction with other medicinal products and other forms of interactions

Folic acid may reduce plasma concentrations of phenobarbital, phenytoin, and primidone, thereby increasing the risk of epileptic seizures. A similar, but less pronounced, association exists with all anticonvulsants, including sodium valproate, carbamazepine, and barbiturates. Chloramphenicol and co-trimoxazole may affect folate metabolism. Sulfasalazine may reduce the absorption of folic acid. Methotrexate and trimethoprim are specific antifolates. Folic acid may interfere with the toxic and therapeutic effects of methotrexate. Antibacterial agents, oral contraceptives, ethanol, sulfasalazine, cycloserine, glutethimide, and methotrexate may affect folate metabolism. Ethanol and acetylsalicylic acid may increase the elimination of folic acid. Folic acid enhances the metabolism of phenytoin. Concomitant use of cholestyramine and folic acid may lead to reduced or altered absorption. Therefore, the drug should be taken 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.

Folates enhance the effectiveness of lithium. Nitrous oxide can cause acute folic acid deficiency. Avoid simultaneous combination with fluorouracil. Antacid preparations containing aluminium or magnesium may reduce the 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. Folic acid deficiency may be caused by drugs such as oral contraceptives, antituberculosis agents, alcohol, and folic acid antagonists such as pyrimethamine, triamterene, trimethoprim, and sulfonamides.

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

Special precautions for use.

The medicinal product should be administered with caution to patients with anemias of unknown etiology and vitamin B12 deficiency, since folic acid may interfere with the diagnosis of pernicious anemia by improving hematological manifestations of the disease, while allowing neurological complications to progress. Vitamin B12 deficiency may result from undiagnosed megaloblastic anemia, particularly in children, pernicious anemia, or macrocytic anemia of unknown etiology; another cause of cobalamin deficiency may be a strict vegetarian diet. In cases of pernicious anemia, the drug should be used only in combination with cyanocobalamin, as 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.

Caution is advised when administering folic acid to patients who may have folate-dependent tumors.

Prolonged use of folic acid, especially in high doses, is not recommended due to the risk of decreased serum cyanocobalamin concentration.

During treatment with folic acid, regular monitoring of blood parameters is required.

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

The preparation contains glucose; therefore, if a patient has known intolerance to certain sugars, he or she should consult a physician before taking this medicinal product.

Use during pregnancy or breastfeeding.

This medicinal product is not intended for healthy pregnant women. The drug is prescribed to pregnant women with folic acid deficiency and to women at risk who are planning pregnancy, for the prevention of congenital fetal abnormalities: neural tube defects (hydrocephalus, encephalocele, cleft palate, cleft lip).

The drug may be used during breastfeeding at recommended doses. Folic acid passes into breast milk.

Folic acid deficiency or impaired folic acid metabolism is associated with the development of congenital defects and certain neural tube defects. Interference with folic acid metabolism or folic acid deficiency caused by certain medicinal products (e.g., anticonvulsants, antineoplastic agents) in early pregnancy may lead to congenital anomalies. Lack of the vitamin or its metabolites may also lead to spontaneous abortion and intrauterine growth retardation.

Ability to influence reaction rate when driving or operating machinery.

When used appropriately, folic acid does not affect the ability to drive a vehicle or operate machinery.

Dosage and Administration

For therapeutic purposes, the drug is prescribed only to adults at a dose of 2*–5 mg per day. The maximum daily dose is 5 mg (1 tablet). The treatment course lasts 20–30 days. It is recommended to conduct 2*–3 courses with a one-month interval between them. Long-term use of the drug is recommended to be combined with vitamin B12 (cyanocobalamin) supplementation.

For women at risk who are planning pregnancy, and for pregnant women with folic acid deficiency, to prevent the development of neural tube defects in the fetus, administer 5 mg (1 tablet) once daily, daily for 4 weeks prior to conception and continue throughout the first 3 months of pregnancy.

For prevention of folic acid deficiency associated with unbalanced or inadequate nutrition: 2*–5 mg per day. The treatment course is 20–30 days.

One month after completing a treatment course, repeating the course is recommended.

For megaloblastic anemia, administer 5 mg (1 tablet) of folic acid daily for 4 months (the recommended preventive dose is 2* mg per day).

Patients with sprue, macrocytic anemia, malabsorption, or inflammatory bowel diseases are recommended to take 5–15 mg (1–3 tablets) per day.

For celiac disease, a daily dose of 5–15 mg is recommended.

For treatment of male infertility due to impaired spermatogenesis (oligospermia), a daily dose of 5 mg (1 tablet) is recommended. The duration of treatment should be determined individually by the physician.

*Administer folic acid at the appropriate dosage.

Children

Do not use in children.

Overdose

No cases of overdose have been reported. Administration in very high doses is not expected to harm the patient.

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: Discontinue the drug and provide symptomatic therapy.

Adverse reactions.

The medicinal product is well tolerated.

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

Immune system disorders: hypersensitivity reactions, including erythema, skin rash, pruritus, urticaria, dyspnea due to bronchospasm, arterial hypotension, anaphylactic reactions, including shock.

Nervous system disorders: chills, sleep disturbances, seizures.

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

Reporting of adverse reactions after marketing authorization is highly important. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Storage conditions.

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

Keep out of reach and sight of children.

Packaging. 10 tablets in a blister. 3 or 5 blisters per carton.

25 tablets in a blister. 2 blisters per carton.

Prescription status. Prescription only.

Manufacturer.

JSC "VITAMINS".

Address of manufacturer and location of business activity.

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

Marketing Authorization Holder.

JSC "VITAMINS".

Address of Marketing Authorization Holder.

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