FOLIC ACID- folic acid tablet
Cardinal Health
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Folic Acid
DESCRIPTION
FOLIC ACID TABLETS, USP
Rev. 02/10
Rx Only
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 dry place protected from light.
The structural formula is as follows:
The molecular formula is C19H19N7O6, and the molecular weight is 441.40.
Each tablet for oral administration contains folic acid 1 mg and the following
inactive ingredients: colloidal silicon dioxide, lactose monohydrate,
microcrystalline cellulose, sodium starch glycolate and stearic acid.
CLINICAL PHARMACOLOGY
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 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
INDICATIONS AND USAGE:
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.
CONTRAINDICATIONS
CONTRAINDICATIONS:
Folic acid is contraindicated in patients who have shown previous intolerance
to the drug.
WARNINGS
WARNINGS:
Administration of folic acid alone is improper therapy for pernicious anemia
and other megaloblastic anemias in which vitamin B12 is deficient.
PRECAUTIONS
General
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.
Interactions
Drug Interactions:Drug InteractionsThere 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
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 EffectsPregnancy – 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
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 or prolonged diarrhea.
ADVERSE REACTIONS
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 of folic acid daily for 1
month. Other side effects reported in patients receiving 15 mg daily include
altered sleep patterns, difficulty in concentrating, irritability, over-activity,
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.
To report SUSPECTED ADVERSE REACTIONS, contact West-ward
Pharmaceutical Corp. at 1-877-233-2001, or the FDA at 1-800-FDA-1088
or www.fda.gov/medwatch.
OVERDOSAGE
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.
DOSAGE AND ADMINISTRATION
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 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 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 SUPPLIED
HOW SUPPLIED:
Folic Acid Tablets USP, 1 mg are Light Yellow, Round, biconvex tablets
debossed “I” on the left side of the bisect and “G” on the right side of bisect on
one side and “210” on other; supplied in bottles of 100 (NDC 0143-9717-01)
and 1000 (NDC 0143-9717-10) .
Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature].
Protect from light and moisture.
Dispense in a tight, light-resistant container as defined in the USP using a
child-resistant closure.
Manufactured by:
InvaGen Pharmaceuticals, Inc.
Hauppauge, NY 11788
Distributed by:
West-ward Pharmaceutical Corp.
Eatontown, NJ 07724
Revised February 2010
Folic Acid Tablets USP, 1 mg are available from Cardinal Health in unit
dose cartons of 30.
Cardinal Health
Zanesville, OH 43701
OI82251010
| FOLIC ACID
folic acid tablet |
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| Labeler - Cardinal Health (188557102) |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Cardinal Health | 188557102 | REPACK(55154-7454) | |