Folic Acid

Class: Vitamin B Complex
VA Class: VT102
CAS Number: 59-30-3

Introduction

Water-soluble, B complex vitamin.^a

Uses for Folic Acid

Anemia

Treatment of megaloblastic anemias due to folic acid deficiency as may be seen in tropical or nontropical sprue, nutritional anemias, and in anemias of pregnancy, infancy, and childhood.^a

Dietary Requirements

Adequate intake of folate needed to prevent megaloblastic changes in the bone marrow and other rapidly dividing cells.¹⁴⁰

Adequate intake of folate can be accomplished through consumption of foodstuffs, including folate-fortified foodstuffs, use of dietary supplements, or both.¹⁴⁰

Prevention of Neural Tube Defects

Prophylactic therapy before and during pregnancy to reduce the risk of fetal neural tube defects, including spina bifida, anencephaly, and encephalocele.^{101 103 104 105 106 109 111 116 118 119 120 121 123 130 132 134 140 148}

Cardiovascular Risk Reduction

No important benefit or harm of folic acid supplementation on the risk of cardiovascular disease, coronary heart disease, stroke, or all-cause mortality in patients with vascular disease.¹⁴⁷

Folic Acid Dosage and Administration

Administration

Usually administered orally.^{a b} May be administered by IM, sub-Q, or IV injection when oral administration is not feasible or when malabsorption is suspected.^b However, most individuals with malabsorption are able to absorb oral folic acid.^a

Dosage

Dosage of sodium folate injection is expressed in terms of folic acid.^b

The Recommended Dietary Allowance (RDA) is expressed in terms of dietary folate equivalents/day.¹⁴⁰ Dietary food folate equivalents (DFE) are calculated as follows: 1 mcg of dietary folate equivalent = 1 mcg of food folate = 0.5 mcg of folic acid taken in the fasting state = 0.6 mcg of folic acid taken with food.¹⁴⁰

Pediatric Patients

Anemia

Oral or Parenteral

Up to 1 mg folic acid daily; some patients may require larger doses.^{a b}

Usual maintenance dosage: 0.1 mg daily for infants, 0.3 mg daily for children <4 years of age, 0.4 mg daily for children ≥4 years of age.^{a b}

Higher maintenance dosages may be required in patients with hemolytic anemia, chronic infections, and those receiving anticonvulsants.^{a b}

Dietary Requirements

Oral

The Adequate Intake (AI) of folate for healthy infants <6 months of age is 65 mcg daily and for those 6–12 months of age is 80 mcg daily.¹⁴⁰

The RDA for healthy children 1–3, 4–8, 9–13, or 14–18 years of age is 0.15, 0.2, 0.3, or 0.4 mg of DFE daily, respectively.¹⁴⁰

Adults

Anemia

Oral or Parenteral

Up to 1 mg folic acid daily; some patients may require larger doses.^{a b}

Usual maintenance dosage: 0.4 mg daily.^{a b}

Usual maintenance dosage for pregnant and lactating women: 0.8 mg daily.^{a b}

Higher maintenance dosages may be required in alcoholics, patients with hemolytic anemia, chronic infections, and patients receiving anticonvulsants.^{a b}

Dietary Requirements

Oral

RDA for healthy adults: 0.4 mg DFE daily.¹⁴⁰

RDA for lactating women: 0.5 mg DFE daily.¹⁴⁰ Folate intake exceeding this RDA may be needed by mothers nursing more than one infant.¹⁴⁰

Prevention of Neural Tube Defects

Oral

National Academy of Sciences: 0.4 mg of folic acid daily through fortified foods and/or supplements in addition to food folate consumed from a varied diet recommended for women of childbearing potential.¹⁴⁰

The US Preventive Services Task Force: 0.4–0.8 mg of folic acid daily from supplements; initiate 1 month before conception and continue during the first 2–3 months of pregnancy.¹⁴⁸

For women with a history of prior pregnancy complicated by neural tube defects: 4 mg folic acid daily initiated 1 month before and continued for 3 months after conception.^c Such women should maintain the lower level of folic acid intake (i.e., 0.4 mg daily) during other periods of continued childbearing potential.^c

RDA for pregnant women: 0.6 mg DFE daily.¹⁴⁰ Folate intake exceeding this RDA may be needed by women who are pregnant with more than one fetus.¹⁴⁰

Cautions for Folic Acid

Contraindications

• 
  

  Known intolerance.^a

  
  

Warnings/Precautions

Warnings

Pernicious Anemia/Undiagnosed Anemia

Not indicated for pernicious anemia and other megaloblastic anemias due to vitamin B₁₂ deficiency.^{a b} Do not use in patients with undiagnosed anemia since folic acid may obscure the diagnosis of pernicious anemia by alleviating hematologic manifestations while allowing neurologic complications to progress.^{a b}

Sensitivity Reactions

Allergic reactions (erythema, rash, itching, general malaise, bronchospastic respiratory difficulty, anaphylaxis) reported rarely.^a

Specific Populations

Pregnancy

Category A.^a

Lactation

Distributed into milk.^a

Common Adverse Effects

Relatively nontoxic.^a

Interactions for Folic Acid

Administration of phenytoin, primidone, barbiturates, methotrexate, nitrofurantoin, alcohol, or pyrimethamine may result in folate deficiency.^a

Phenytoin

Possible increase in seizure frequency.^a

Chloramphenicol

Possible delayed response to folic acid^c

Folic Acid Pharmacokinetics

Absorption

Bioavailability

Well absorbed from the GI tract.^a Synthetic folic acid is almost 100% bioavailable following oral administration in fasting individuals; folate in food is about 50% bioavailable.¹⁴⁰

Food

Synthetic folic acid is 85–100% bioavailable following oral administration with a meal.¹⁴⁰

Distribution

Extent

Distributed into all body tissues including the CNS; stored mainly in the liver.^a

Elimination

Metabolism

Metabolized in the liver.^a

Elimination Route

Up to 90% of a dose in urine; small amounts in feces.^a

Stability

Storage

Oral

Tablets

15–30°C.^a

Parenteral

Injection

15–30°C.^b

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Amino acids 4.25%, dextrose 25%
Dextrose 20% in water
Incompatible
Dextrose 40 or 50% in water
Variable
Fat emulsion 10%, IV

Drug Compatibility

Y-Site CompatibilityHID

Compatible
Famotidine

ActionsActions

• 
  

  Folic acid is prepared synthetically.^{a 140} Naturally occurring conjugates of folic acid (food folate; pteroylpolyglutamates) are present in a wide variety of foods, particularly liver, kidneys, yeast, leafy green vegetables, other vegetables, citrus fruits and juice, and legumes.¹⁴⁰

  
  


• 
  

  An exogenous source of folate is required for nucleoprotein synthesis and the maintenance of normal erythropoiesis.^a

  
  


• 
  

  Folic acid is not metabolically active as such, but is the precursor of tetrahydrofolic acid which is involved as a cofactor for 1-carbon transfer reactions in the biosynthesis of purines and thymidylates of nucleic acids.^a

  
  


• 
  

  Folate supplementation before and during pregnancy associated with a reduction in risk for fetal neural tube defects.¹⁴⁰

  
  

Advice to Patients

• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{a b}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{a b}

  
  


• 
  

  Importance of informing patients of other important precautionary information.^{a b} (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Folic Acid

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Bulk	Powder*
Oral	Tablets	0.4 mg*	Folic Acid Tablets
		0.8 mg*	Folic Acid Tablets
		1 mg*	Folic Acid Tablets

Sodium Folate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection	equivalent to folic acid 5 mg/mL	Folic Acid Injection

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 05/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Folic Acid 400MCG Tablets (MAJOR PHARMACEUTICALS): 250/$12.99 or 500/$17.95

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions January 01, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

100. National Research Council Food and Nutrition Board Subcommittee on the Tenth Edition of the RDAs. Recommended dietary allowances. 10th ed. Washington, DC: National Academy Press; 1989:150-8.

101. Centers for Disease Control and Prevention. Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR Morb Mortal Wkly Rep. 1992; 41(RR-14):1-7.

102. Centers for Disease Control and Prevention. Use of folic acid for prevention of spina bifida and other neural tube defects—1983-1991. MMWR Morb Mortal Wkly Rep. 1991; 40:513-6. [IDIS 283697] [PubMed 2072886]

103. Committee on Genetics. Folic acid for the prevention of neural tube defects. Pediatrics. 1993; 92:493-4. [IDIS 319942] [PubMed 8361816]

104. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the medical research council vitamin study. Lancet. 1991; 338:131-7. [IDIS 283551] [PubMed 1677062]

105. Anon. Folic acid and neural tube defects. Lancet. 1991; 338:153-4. [PubMed 1677069]

106. Laurence KM. Folic acid to prevent neural tube defects. Lancet. 1991; 338:379. [IDIS 284113] [PubMed 1677712]

107. Taguchi H. Folic acid to prevent neural tube defects. Lancet. 1991; 338:506. [IDIS 284487] [PubMed 1678458]

108. Reynolds EH. Folic acid to prevent neural tube defects. Lancet. 1991; 338:505-6. [IDIS 284483] [PubMed 1678457]

109. Jick H, Jick SS, Milunsky A et al. Vitamins to prevent neural tube defects. Lancet. 1991; 338:639. [PubMed 1679181]

110. Super M, Summers EM, Meylan B. Preventing neural tube defects. Lancet. 1991; 338:775-6.

111. Grant A, Chalmers I. Vitamins to prevent neural tube defects. Lancet. 1991; 338:894.

112. Lucock MD, Wild J, Hartley R et al. Vitamins to prevent neural tube defects. Lancet. 1991; 338:894-5.

113. Davies DP. Vitamins to prevent neural tube defects. Lancet. 1991; 338:895. [PubMed 1681258]

114. Smithells RW, Sheppard S, Schorah CJ. Folic acid to prevent neural tube defects. Lancet. 1991; 338:379-8. [IDIS 284113] [PubMed 1677712]

115. Scott JM, Kirke P, O’Broin et al. Folic acid to prevent neural tube defects. Lancet. 1991; 338:505. [IDIS 284483] [PubMed 1678457]

116. Jukes TH. Vitamins to prevent neural tube defects. Lancet. 1991; 338:640. [IDIS 284908] [PubMed 1679182]

117. Leeming RJ, Blair JA, Brown SE. Vitamins to prevent neural tube defects. Lancet. 1991; 338:895. [PubMed 1681258]

118. American Academy of Pediatrics. Daily folic acid use reduces birth defects. Elk Grove Village, IL; 1993 Sep 8. Press release.

119. Werler MM, Shapiro S, Mitchell AA. Periconceptional folic acid exposure and risk of occurrent neural tube defects. JAMA. 1993; 269:1257-61. [IDIS 310479] [PubMed 8437302]

120. Oakley GP Jr. Folic acid—preventable spina bifida and anencephaly. JAMA. 1993; 269:1292-3. [IDIS 310481] [PubMed 8437310]

121. Sutcliffe M, Schorah CJ, Perry A et al. Prevention of neural tube defects. Lancet. 1991; 338:379. [IDIS 284113] [PubMed 1677712]

122. Centers for Disease Control and Prevention. Possible adverse effects of folic acid consumption; meeting. Prescription Pharm. 1993; 58:40149.

123. Elwood M. Folic acid prevents neural tube defects. Med J Aust. 1991; 155:579-81. [IDIS 293180] [PubMed 1943950]

124. Holmes LB. Prevention of neural tube defects. J Pediatr. 1992; 120:918-9. [PubMed 1593351]

125. Glanville NT, Cook HW. Folic acid and prevention of neural tube defects. CMAJ. 1992; 146:39. [IDIS 289844] [PubMed 1728351]

126. Milunsky A, Jick H, Jick SS et al. Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of neural tube defects. JAMA. 1989; 262:2847-52. [IDIS 260709] [PubMed 2478730]

127. Mills JL, Rhoads GG, Simpson JL et al. Vitamins during pregnancy and neural tube defects. JAMA. 1990; 263:2747-8. [IDIS 266110] [PubMed 2332916]

128. Shapiro S, Mitchell AA, Werler MM. Vitamins during pregnancy and neural tube defects. JAMA. 1990; 263:2748.

129. Milunsky A, Jick H, Jick SS et al. Vitamins during pregnancy and neural tube defects. JAMA. 1990; 263:2748-9.

130. Vergel RG, Sanchez LR, Heredero BL et al. Primary prevention of neural tube defects with folic acid supplementation: cuban experience. Prenatal Diagn. 1990; 10:149-52.

131. Bower C, Stanley FJ. Dietary folate as a risk factor for neural-tube defects: evidence from a case-control study in western Australia. Med J Aust. 1989; 150:613-9. [IDIS 270449] [PubMed 2725375]

132. Griffin JP. Vitamins and neural tube defects. BMJ. 1988; 296:430. [PubMed 3125934]

133. World Health Organization. Folic acid and spina bifida. WHO Drug Info. 1993; 7:106-8.

134. Wald NJ, Bower C. Folic acid, pernicious anaemia, and prevention of neural tube defects. Lancet. 1994; 343:307. [IDIS 325444] [PubMed 7905138]

135. Beresford SAA. Annotation: how do we get enough folic acid to prevent some neural tube defects? Am J Public Health. 1994; 84:348-50.

136. US Food and Drug Administration. [FDA proposes that folic acid be added to flour, breads, and other grains.] Rockville, MD; 1993 Oct 8. Press release.

137. Foulke J (US Food and Drug Administration). Folic acid to fortify U.S. food products to prevent birth defects. Rockville, MD; 1996 Feb 29. Press Release No. P96-3.

138. Food and Drug Administration. Food additives permitted for direct addition to food for human consumption; folic acid (folacin). 21 CFR Part 172. Final rule. [Docket No. 91N-100F]. Fed Regist. 1996; 61:8797-8807.

139. Tucker KL, Mahnken B, Wilson PWF et al. Folic acid fortification of the food supply: potential benefits and risks for the elderly population. JAMA. 1996; 276:1879-85. [IDIS 376692] [PubMed 8968013]

140. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes of the Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B₆, folate, vitamin B₁₂, pantothenic acid, biotin, and choline. Washington, DC: National Academy Press; 1998. (Prepublication copy uncorrected proofs.)

141. Ubbink JB. Should all elderly people receive folate supplements? Drugs Aging. 1998; 13:415-20.

142. McCully KS. Homocysteine, folate, vitamin B₆, and cardiovascular disease. JAMA. 1998; 279:392-3. [IDIS 399272] [PubMed 9459475]

143. Rimm EB, Willett WC, Hu FB et al. Folate and vitamin B₆ from diet and supplements in relation to risk of coronary heart disease among women. JAMA. 1998; 279:359-64. [IDIS 399268] [PubMed 9459468]

144. Malinow MR, Duell PB, Hess DL et al. Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N Engl J Med. 1998; 338:1009-15. [IDIS 402456] [PubMed 9535664]

145. Homocysteine Lowering Trialists’ Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. BMJ. 1998; 316:894-8. [IDIS 404785] [PubMed 9569395]

146. The Homocysteine Studies Collaborative. Homocysteine and risk of ischemic heart disease and stroke; a meta-analysis. JAMA. 2002; 288:2015-22. [PubMed 12387654]

147. Bazzano LA, Reynolds K, Holder KN et al. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA. 2006; 296: 2720-26. [PubMed 17164458]

148. US Preventive Services Task Force. Folic acid for the prevention of neural tube defects: US Preventive Services Task Force recommendation statement. Ann Inter Med. 2009; 150:626-31.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:746-8.

a. Danbury Pharmacal. Folic acid tablets, USP prescribing information. Danbury, CT: 1998 Jul.

b. Lederle Laboratories. Folvite folic acid tablets-parenteral solution prescribing inforation (dated Jan 1988). In: Physicians’ desk reference. 43rd edition. Montevale, NJ: Medical Economics Company Inc; 1989:1120

c. AHFS drug information 2003. McEvoy GK, ed. Folic Acid. Bethesda, MD: American Society of Health-System Pharmacists; 2003: page 3500-2.

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