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Folic Acid

Pronunciation

Dosage Form: tablet

Folic Acid

Tablets, USP

Folic Acid Description

Folic Acid, N-p-[[2-amino-4-hydroxy-6-pteridinyl] 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 a peptide linkage to glutamic acid. Conjugates of
Folic Acid are present in a wide variety of foods, particularly liver, kidneys, yeast, and leafy
green vegetables. Commercially available Folic Acid 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 may be prepared with the aid of sodium hydroxide or
sodium carbonate, thereby forming the soluble sodium salt of Folic Acid (sodium folate).
Aqueous solutions of Folic Acid 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 structural formula of Folic Acid is as follows:


C19H19N7O6 M.W. 441.40

Each tablet, for oral administration, contains 1 mg Folic Acid.

Folic Acid Tablets, USP 1 mg contain the following inactive ingredients: lactose monohydrate,
microcrystalline cellulose, sodium starch glycolate and magnesium stearate.

Folic 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 of 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 thymidylate synthesis in patients with Folic Acid
deficiency is thought to account for the defective deoxyribonucleic acid (DNA) synthesis that
leads to megaloblast formation and megaloblastic and macrocytic anemias.


Folic Acid is absorbed rapidly from the small intestine, primarily from the proximal portion.
Naturally occurring conjugated folates are reduced enzymatically to Folic Acid in the
gastrointestinal 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 N5 or N10 positions with formyl, hydroxymethyl, methyl,
or formimino groups. N5-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 cerebro-spinal
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 μg 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 μg/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 for Folic Acid

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

Warning

Administration of Folic Acid alone is improper therapy for pernicious anemia and other
megaloblastic anemias in which vitamin B12 is deficient.

Precautions

General
Folic Acid in doses above 0.1 mg 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 B12 may prevent, halt, or improve the neurologic changes caused by
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 suppress 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

Teratogenic Effects
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 μg daily), or in those with
infections or prolonged diarrhea.

Adverse Reactions

Allergic sensitization has been reported following both oral and parenteral administration of
Folic Acid.


Folic Acid is relatively nontoxic in man. Rare instances of allergic responses to Folic Acid
preparations have been reported and have included erythema, skin rash, itching, general
malaise, and respiratory difficulty due to bronchospasm. One patient experienced symptoms
suggesting anaphylaxis following injection of the drug. Gastrointestinal side effects, including
anorexia, nausea, abdominal distention, flatulence, and a bitter or bad taste, have been
reported in patients receiving 15 mg Folic Acid daily for 1 month. Other side effects reported
in patients receiving 15 mg daily include altered sleep patterns, difficulty in concentrating,
irritability, overactivity, excitement, mental depression, confusion, and impaired judgment.
Decreased vitamin B12 serum levels may occur in patients receiving prolonged Folic Acid
therapy.


In an uncontrolled study, orally administered Folic Acid was reported to increase the incidence
of seizures in some epileptic patients receiving phenobarbital, primidone, or
diphenylhydantoin. Another investigator reported decreased diphenylhydantoin serum levels
in folate-deficient patients receiving diphenylhydantoin who were treated with 5 mg or 15 mg
of Folic Acid daily.

Overdosage

Except during pregnancy and lactation, Folic Acid should not be given in therapeutic doses
greater than 0.4 mg daily until pernicious anemia has been ruled out. Patients with pernicious
anemia receiving more than 0.4 mg of Folic Acid daily who are inadequately treated with
vitamin B12 may show reversion of the hematologic parameters to normal, but neurologic
manifestations due to vitamin B12 deficiency will progress. Doses of Folic Acid exceeding the
Recommended Dietary Allowance (RDA) should not be included in multivitamin preparations;
if therapeutic amounts are necessary, Folic Acid should be given separately.

Folic Acid Dosage and Administration

Oral administration is preferred. Although most patients with malabsorption cannot absorb
food folates, they are able to absorb Folic Acid given orally. Parenteral administration is not
advocated but may be necessary in some individuals (e.g., patients receiving parenteral or
enteral alimentation). Doses greater than 0.1 mg should not be used unless anemia due to
vitamin B12 deficiency has been ruled out or is being adequately treated with a cobalamin.
Daily doses greater than 1 mg do not enhance the hematologic effect, and most of the excess
is excreted unchanged in the urine. The usual therapeutic dosage in adults and children
(regardless of age) is up to 1 mg daily. Resistant cases may require larger doses. When
clinical symptoms have subsided and the blood picture has become normal, a daily
maintenance level should be used, i.e., 0.1 mg for infants and up to 0.3 mg for children under
4 years of age, 0.4 mg for adults and children 4 or more years of age, and 0.8 mg for
pregnant and lactating women, but never less than 0.1 mg/day. Patients should be kept
under close supervision and adjustment of the maintenance level made if relapse appears
imminent.


In the presence of alcoholism, hemolytic anemia, anticonvulsant therapy, or chronic infection,
the maintenance level may need to be increased.

How is Folic Acid Supplied

Folic Acid Tablets, USP 1 mg are yellow, functionally scored, round, standard convex debossed
with “B”, “-“ and “01” on one side and plain on the other side supplied in bottles of 30 and
500.


30’s: 58657-850-30
500’s: 58657-850-50


Dispense in well-closed container with child-resistant closure.


Store 20°-25°C (68°-77°F). [See USP controlled room temperature.]

Manufactured by:
ANSHI PHARMACEUTICAL
(ZHONGSHAN) INC.
Zhongshan, Guangdong 528437
P.R. China


Manufactured for:
Method Pharmaceuticals, LLC
Arlington, TX 76006


Rev Date: 2/16

Principal Display Panel

Folic Acid 
Folic Acid tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:58657-850
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Folic Acid (Folic Acid) Folic Acid 1 mg
Inactive Ingredients
Ingredient Name Strength
LACTOSE MONOHYDRATE  
SODIUM STARCH GLYCOLATE TYPE A CORN  
MAGNESIUM STEARATE  
CELLULOSE, MICROCRYSTALLINE  
Product Characteristics
Color yellow Score no score
Shape ROUND Size 8mm
Flavor Imprint Code B;1
Contains         
Packaging
# Item Code Package Description
1 NDC:58657-850-30 30 TABLET in 1 BOTTLE
2 NDC:58657-850-50 500 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA091145 02/09/2016
Labeler - Method Pharmaceuticals, LLC (060216698)
Revised: 04/2016
 
Method Pharmaceuticals, LLC
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