Folic Acid (Folate Sodium)


General Monograph,

Pteroylglutamic Acid

Folate Sodium

Anemia Therapy

Pharmacology: Folic acid is a B complex vitamin. After absorption from the gastrointestinal tract, folic acid is hepatically converted to tetrahydrofolic acid which is a cofactor in the biosynthesis of purines and thymidylates of nucleic acids. An exogenous source of folic acid is necessary for the maintenance of normal erythropoiesis.

Folic acid deficiency can lead to meagloblastic and macrocytic anemias, as a result of impairment of thymidylate synthesis.

Folic acid occurs in a variety of foods in the form of polyglutamate conjugates. Folic acid found in oral or injectable pharmaceutical preparations is synthetically derived.

Studies have provided strong scientific support for periconceptual prophylaxis with folic acid in reducing the risk of neural tube defects.

Folic acid supplementation has been shown to reduce elevated fasting plasma homocysteine levels, one of the known risk factors for atherosclerotic disease. Studies measuring clinical outcomes are in progress and will establish whether such therapy will result in a reduction of cardiovascular risk.

Pharmacokinetics: Folic acid polyglutamates from food sources are enzymatically hydrolyzed in the gastrointestinal tract to monoglutamates prior to absorption, which occurs mainly in the proximal small intestine. In the presence of malabsorption syndrome, folic acid from oral supplements will still be absorbed, whereas absorption of folic acid from food sources may be impaired.

Following absorption of 1 mg or less, folic acid is converted in the liver and plasma to its metabolically active form tetrahydrofolic acid, which is then distributed into all body tissues. Normal serum folate concentrations range from 0.016 to 0.021 µg/mL. The liver contains about 50% of total body folate stores. Larger doses of folic acid may escape metabolism by liver and appear in the blood mainly as folic acid. Following oral administration of single 0.1 to 0.2 mg doses of folic acid in healthy adults, only a trace amount of the drug appears in urine. Following administration of large doses, the renal tubular reabsorption maximum is exceeded, and excess folate is excreted unchanged in urine. After doses of about 2.5 to 5 mg, about 50% of a dose is excreted in urine and after a 15 mg dose, up to 90% may be recovered in urine. Small amounts of orally administered folic acid have been recovered from feces.

Indications: Folic acid is used in the treatment of megaloblastic and macrocytic anemias caused by folate deficiency. It is also used in the treatment of megaloblastic anemias of pregnancy, infancy and childhood, as well as megaloblastic anemias associated with primary liver disease, alcoholic cirrhosis, intestinal strictures, anastomoses or sprue. In large doses, folic acid is used in the treatment of tropical sprue.

There is strong evidence that prophylactic therapy with folic acid, prior to and during pregnancy, can reduce the risk of fetal neural tube defects. Expert groups recommend that all women of child bearing potential, whether planning pregnancy or not, should maintain an adequate daily intake of folic acid (see Dosage).

Folic acid is not effective in reversing the effects of folic acid reductase inhibitors such as methotrexate, for which leucovorin calcium (folinic acid) must be used.

Precautions: Use only as an adjunct to treatment with vitamin B12 whenever pernicious anemia is present or suspected. The use of folic acid in pernicious anemia without adequate vitamin B12 therapy may result in hematologic improvement, while neurologic manifestations continue to progress.

Folic acid is not effective as an antidote or in the rescue treatment of overdosage of folic acid antagonists such as methotrexate.

Drug Interactions : Folic acid therapy in folate deficient individuals may decrease serum levels of phenytoin.

Drugs which may cause folate deficiency include phenytoin, isoniazid, primidone, barbiturates, oral contraceptives, ethanol, sulfasalazine, cycloserine, glutethamide, methotrexate, pyrimethamine, trimethoprin and triamterene.

When cholestyramine and folic acid are administered together, there may be a reduction or delay in folic acid absorption. If concomitant therapy is required, folic acid should be administered at least 1 hour before or 4 to 6 hours after cholestyramine.

Pregnancy: Pregnant women are more prone to develop folate deficiency which can lead to complications and fetal abnormalities (see Pharmacology).

Lactation: Folic acid is actively excreted in human breast milk. Adverse effects in breast-fed infants have not been documented with intake of normal daily requirements of folic acid during lactation.

Adverse Effects: Folic acid is relatively nontoxic but has rarely caused allergic reactions including erythema, pruritus and/or urticaria. High doses (e.g. 15 mg/day) have rarely been associated with seizures, psychosis and gastrointestinal symptoms.

Dosage: To prevent deficiency, adequate dietary intake of folic acid is preferred over supplementation whenever possible. For a listing of food sources of folic acid, see Vitamin Food Sources in the Clin-Info section. For information on the daily requirements of folic acid, see Recommended Nutrient Intake in the Clin-Info section.

Treatment of Deficiency: Oral: The usual therapeutic dose of folic acid for adults and children is 0.25 to 1 mg daily; however, some patients may require higher doses. Within the first 48 hours of treatment, the bone marrow begins to become normoblastic. Reticulocytosis begins within 2 to 5 days. To maintain a normoblastic marrow, lower daily maintenance doses of folic acid are used: adults and children 4 years and over, 0.4 mg; children up to 4 years, 0.3 mg; infants, 0.1 mg. Higher maintenance doses may be required in alcoholics, patients with hemolytic anemia or chronic infections, or in patients taking anticonvulsants.

Higher doses have been recommended for the treatment of tropical sprue: 3 to 15 mg daily.

Parenteral: When the oral route is not feasible, an equivalent dose of folic acid may be given by i.v., s.c. or deep i.m. injection. However, most patients with malabsorption syndrome are still able to absorb oral folic acid supplements.

Prophylaxis vs Neural Tube Defects (NTD): The Society of Obstetricians and Gynaecologists of Canada, in its 1993 Policy Statement, recommended that all women of child bearing potential, whether planning pregnancy or not, should consider maintaining a folic acid intake of at least 0.4 mg daily, either in the diet or as a supplement. Pregnant women with no previous history of fetal NTD and no other predisposing factors are advised to maintain an intake of at least 0.4 mg daily until 10 to 12 weeks after last menstrual period.

Women with a history of pregnancy complicated by NTD are considered at high risk for recurrence and are advised to consider taking 4 mg folic acid daily when not using reliable birth control (or at least 2 to 4 weeks prior to conception), continuing until 10 to 12 weeks after last menstrual period.

Women with no previous history of NTD-affected pregnancy but who may be at increased risk due to 1tdegree relative (child, sibling or parent) with NTD, or for medical reasons such as type I diabetes or therapy with valproic acid or carbamazepine, are advised to consider taking 1 to 4 mg folic acid daily while not using reliable birth control, continuing for 10 to 12 weeks after last menstrual period.

*Products with strengths less than 1 mg are available without a prescription.

FOLIC ACID *General Monograph,Pteroylglutamic AcidFolate SodiumAnemia Therapy

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