Folic Acid (folic acid 1 mg) Dailymed

Rx only

Description

Folic acid, USP, N- [ p-[[(2-amino-4- hydroxy-6-pteridinly) methyl]-amino] benzoyl]-L-glutamic acid, is a B complex vitamin containing a pteridine moiety linked by a methylene bridge to para-aminobenzoic acid, which is joined by peptide linkage to a glutamic acid. Conjugates of folic acid, USP are present in a wide variety of foods, particularly liver, kidneys, yeast, and leafy green vegetables. Commercially available folic acid, USP is prepared synthetically. Folic Acid occurs as a yellow or yellowish-orange crystalline powder and is very slightly soluble in water and insoluble in alcohol. Folic Acid is readily soluble in dilute solutions of alkali hydroxides and carbonates, and solutions of the drug maybe prepared with the aid of sodium hydroxide or sodium carbonate, thereby forming the soluble salt of folic acid, USP (sodium folate). Aqueous solutions of folic acid, USP are heat sensitive and rapidly decompose in the presence of light and/or riboflavin; solutions should be stored in a cool place protected from light.

The structure formula of folic acid, USP is as follows:

C ₁₉H ₁₉N ₇O ₆                                                               M.W.441.40

Each tablet, for oral administration, contains 1mg folic acid, USP.

Folic acid tablets, USP 1mg contain the following inactive ingredients: lactose monohydrate microcrystalline cellulose, sodium starch glycolate and stearic acid.

Clinical Pharmacology

Folic Acid acts on megaloblastic bone marrow to produce a normoblastic marrow.

In man, an exogenous source of folate is required for nucleoprotein synthesis and the maintenance or normal erythropoiesis. Folic acid is the precursor of tetrahydrofolic acid, which is involved as a cofactor for transformylation reactions in the biosynthesis of purines and thymidylates of nucleic acids. Impairment of tymidylates synthesis in patients with folic acid deficiency is thought to account for the defective deoxyribonucleic acid (DNA) synthesis that leads to megaloblast information and megaloblastic and macrocytic anemias.

Folic Acid is absorbed rapidly from the small intestines, primarily from the proximal portion. Naturally occurring conjugated folates are reduced enzymatically to folic acid in the gastro intestinal tract prior to absorption. Folic acid appears in the plasma approximately 15 to 30 minutes after an oral dose; peak levels are generally reached within 1 hour. After intravenous administration, the drug is rapidly cleared from the plasma. Cerebrospinal fluid levels of folic acid are several times greater than serum levels of the drug. Folic Acid is metabolized in the liver to 7, 8-dihydrofolic acid and eventually to 5,6,7,8-tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide (DPNH) and folate reductases. Tetrahydrofolic acid is linked in the N ₅ or N ₁₀ positions with formyl, hydroxymethyl, or methyl, or formimino groups. N ₅-formyltetrahydrofolic acid is leucovorin. Tetrahydrofolic acid derivatives are distributed to all body tissues but are stored primarily in the liver. Normal serum levels of total folate have been reported to be 5 to 15 ng/mL; normal cerebrospinal fluid levels are approximately 16 to 21 ng/mL. Normal erythrocyte folate levels have been reported to range from 175 to 316 ng/mL. In general, folate serum levels below 5 ng/mL indicate folate deficiency, and levels below 2 ng/mL usually result in megaloblastic anemia.

After a single oral dose of 100 mcg of folic acid in a limited number of normal adults, only a trace amount of the drug appeared in the urine. An oral dose of 5 mg in 1 study and a dose of 40 mcg/kg of body weight in another study resulted in approximately 50% of the dose appearing in the urine. After a single oral dose of 15 mg, up to 90% of the dose was recovered in the urine. A majority of the metabolic products appeared in the urine after 6 hours; excretion was generally complete within 24 hours. Small amounts of orally administered folic acid have also been recovered in the feces. Folic Acid is also excreted in the milk of lactating mothers.

Indications And Usage

Folic acid, USP is effective in the treatment of megaloblastic anemias due to a deficiency of folic acid, USP (as may be seen in tropical or nontropical sprue) and in anemias of nutritional origin, pregnancy, infancy, or childhood.

Contraindications

Folic acid, USP is contraindicated in patients who have shown previous intolerance to the drug.

Warning

Administration of folic acid alone is improper therapy for pernicious anemia and other megaloblastic anemias in which vitamin B ₁₂ is deficient.

Precautions

General

Folic Acid in doses above 0.1mg daily may obscure pernicious anemia in that hematologic remission can occur while neurologic manifestations remain progressive.

There is a potential danger in administering folic acid to patients with undiagnosed anemia, since folic acid may obscure the diagnosis of pernicious anemia by alleviating the hematologic manifestations of the disease while allowing the neurologic complications to progress. This may result in severe nervous system damage before the correct diagnosis is made. Adequate doses of vitamin B ₁₂ may prevent, halt, or improve the neurologic changes by the pernicious anemia.

Drug Interactions

There is evidence that the anticonvulsant action of phenytoin is antagonized by folic acid. A patient whose epilepsy is completely controlled by phenytoin may require increased doses to prevent convulsions if folic acid is given.

Folate deficiency may result from increased loss of folate, as in renal dialysis and/or interference with metabolism (e.g., folic acid antagonists such as methotrexate); the administration of anticonvulsants, such as diphenylhydantoin, primidone, and barbiturates; alcohol consumption and, especially, alcoholic cirrhosis; and the administration of pyrimethamine and nitrofurantoin.

False low serum and red cell folate levels may occur if the patient has been taking antibiotics such as tetracycline, which suppresses the growth of Lactobacillus casei.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to evaluate carcinogenic potential and studies to evaluate the mutagenic potential or effect on fertility have not been conducted.

Pregnancy

Pregnancy Category A

Folic acid is usually indicated in the treatment of megaloblastic anemias of pregnancy. Folic acid requirements are markedly increased during pregnancy, and deficiency will result in fetal damage (see INDICATIONS AND USAGE ).

Studies in pregnant women have not shown that folic acid increases the risk of fetal abnormalities if administered during pregnancy. If the drug is used during pregnancy, the possibility of fetal harm appears remote. Because studies cannot rule out the possibility of harm, however, folic acid should be used during pregnancy only if clearly needed.

Nursing mothers

Folic acid is excreted in the milk of lactating mothers. During lactation, folic acid requirements are markedly increased; however, amounts present in human milk are adequate to fulfill infant requirements, although supplementation may be needed in low-birth-weight infants, in those who are breast-fed by mothers with folic acid deficiency (50 mcg daily), or in those with infections of prolonged diarrhea.