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Folic Acid

Pronunciation

Pronunciation

(FOE lik AS id)

Index Terms

  • Folacin
  • Folate
  • Pteroylglutamic Acid

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral [preservative free]:

FA-8: 0.8 mg [dye free, sugar free, yeast free]

Generic: 5 mg, 20 mg

Solution, Injection, as sodium folate:

Generic: 5 mg/mL (10 mL)

Tablet, Oral:

Generic: 400 mcg, 800 mcg, 1 mg

Tablet, Oral [preservative free]:

FA-8: 800 mcg [dye free]

Generic: 400 mcg, 800 mcg

Brand Names: U.S.

  • FA-8 [OTC]

Pharmacologic Category

  • Vitamin, Water Soluble

Pharmacology

Folic acid is necessary for formation of a number of coenzymes in many metabolic systems, particularly for purine and pyrimidine synthesis; required for nucleoprotein synthesis and maintenance in erythropoiesis; stimulates WBC and platelet production in folate deficiency anemia. Folic acid enhances the metabolism of formic acid, the toxic metabolite of methanol, to nontoxic metabolites (off-label use).

Absorption

Proximal part of small intestine

Metabolism

Hepatic

Excretion

Urine

Onset of Action

Peak effect: Oral: 0.5-1 hour

Time to Peak

Oral: 1 hour

Use: Labeled Indications

Megaloblastic and macrocytic anemias due to folate deficiency: Treatment of megaloblastic and macrocytic anemias due to folate deficiency

Use: Unlabeled

Adjunctive cofactor therapy in methanol toxicity (alternative to leucovorin calcium); dietary supplement to prevent neural tube defects

Contraindications

Hypersensitivity to folic acid or any component of the formulation

Dosing: Adult

Megaloblastic and macrocytic anemias due to folate deficiency:

Manufacturer’s labeling: Oral, IM, IV, SubQ: Initial: 0.4 to 1 mg/day. Higher doses may be required in resistant cases.

Maintenance dose: 0.4 mg/day

Pregnant and lactating women: Maintenance dose: 0.8 mg/day

Alternate recommendations (off-label dose): Oral: 1 to 5 mg once daily (Cook 2014); doses up to 15 mg once daily have also been recommended (Hoffbrand 2015).

Recommended daily allowance (RDA) (IOM, 1998): Expressed as dietary folate equivalents: Oral: 400 mcg/day

Pregnancy: 600 mcg/day

Lactation: 500 mcg/day

Prevention of neural tube defects (off-label use): Oral:

Females of childbearing potential: 400 to 800 mcg/day (USPSTF 2009)

Females at high risk or with family history of neural tube defects: 4 mg/day (ACOG 2003)

Dosing: Geriatric

Refer to adult dosing. Vitamin B12 deficiency must be ruled out before initiating folate therapy due to frequency of combined nutritional deficiencies: RDA requirements (1999): 400 mcg/day (0.4 mg) minimum.

Dosing: Pediatric

Megaloblastic and macrocytic anemias due to folate deficiency: Oral, IM, IV, SubQ: Initial: 0.4 to 1 mg/day. Higher doses may be required in resistant cases.

Maintenance dose:

Infants: 0.1 mg/day

Children <4 years: Up to 0.3 mg/day

Children ≥4 years, Adolescents, and Adults: Refer to adult dosing.

Adequate intake (AI) (IOM 1998): Expressed as folate equivalents: Oral: Infants:

1 to 6 months: 65 mcg/day

7 to 12 months: 80 mcg/day

Recommended daily allowance (RDA) (IOM 1998): Expressed as dietary folate equivalents: Oral:

Children 1 to 3 years: 150 mcg/day

Children 4 to 8 years: 200 mcg/day

Children 9 to 13 years: 300 mcg/day

Adolescents ≥14 years: Refer to adult dosing.

Extemporaneously Prepared

A 1 mg/mL folic acid oral solution may be made with tablets. Heat 90 mL of purified water almost to boiling. Dissolve parabens (methylparaben 200 mg and propylparaben 20 mg) in the heated water; cool to room temperature. Crush one-hundred 1 mg tablets, then dissolve folic acid in the solution. Adjust pH to 8-8.5 with sodium hydroxide 10%; add sufficient quantity of purified water to make 100 mL; mix well. Stable for 30 days at room temperature (Allen, 2007).

A 0.05 mg/mL folic acid oral solution may be prepared using the injectable formulation (5 mg/mL). Mix 1 mL of injectable folic acid with 90 mL of purified water. Adjust pH to 8-8.5 with sodium hydroxide 10%; add sufficient quantity of purified water to make 100 mL; mix well. Stable for 30 days at room temperature (Nahata, 2004).

Allen LV Jr, "Folic Acid 1-mg/mL Oral Liquid," Int J Pharm Compound, 2007, 11(3):244.Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.

Administration

Oral preferred, but may also be administered by deep IM, SubQ, or IV injection.

IV administration: May administer ≤5 mg dose undiluted over ≥1 minute or may dilute ≤5 mg in 50 mL of NS or D5W and infuse over 30 minutes. May also be added to IV maintenance solutions and given as an infusion.

Dietary Considerations

As of January 1998, the FDA has required manufacturers of enriched flour, bread, corn meal, pasta, rice, and other grain products to add folic acid to their products. The intent is to help decrease the risk of neural tube defects by increasing folic acid intake. Other foods which contain folic acid include dark green leafy vegetables, citrus fruits and juices, and lentils.

Compatibility

Stable in D5W, D20W, NS, fat emulsion 10%; incompatible with D40W, D50W. Do not use with oxidizing and reducing agents or heavy metal ions.

Compatibility in syringe: Incompatible with doxapram.

Storage

Store at 20°C to 25°C (68°F to 77°F); protect from light.

Drug Interactions

Fosphenytoin: Folic Acid may decrease the serum concentration of Fosphenytoin. Monitor therapy

Green Tea: May decrease the serum concentration of Folic Acid. Monitor therapy

PHENobarbital: Folic Acid may decrease the serum concentration of PHENobarbital. Monitor therapy

Phenytoin: Folic Acid may decrease the serum concentration of Phenytoin. Monitor therapy

Primidone: Folic Acid may decrease the serum concentration of Primidone. Additionally, folic acid may decrease concentrations of active metabolites of primidone (e.g., phenobarbital). Monitor therapy

Raltitrexed: Folic Acid may diminish the therapeutic effect of Raltitrexed. Avoid combination

SulfaSALAzine: May decrease the serum concentration of Folic Acid. Monitor therapy

Test Interactions

Falsely low serum concentrations may occur with the Lactobacillus casei assay method in patients on anti-infectives (eg, tetracycline)

Adverse Reactions

Frequency not defined.

Cardiovascular: Flushing (slight)

Central nervous system: Malaise (general)

Dermatologic: Erythema, pruritus, skin rash

Hypersensitivity: Hypersensitivity reaction

Respiratory: Bronchospasm

Warnings/Precautions

Disease-related concerns:

• Anemia: Monotherapy: Not appropriate for monotherapy with pernicious, aplastic, or normocytic anemias when anemia is present with vitamin B12 deficiency.

• Pernicious anemia: Doses >0.1 mg/day may obscure pernicious anemia with continuing irreversible nerve damage progression.

Dosage form specific issues:

• Aluminum: The parenteral product may contain aluminum; toxic aluminum concentrations may be seen with high doses, prolonged use, or renal dysfunction. Premature neonates are at higher risk due to immature renal function and aluminum intake from other parenteral sources. Parenteral aluminum exposure of >4 to 5 mcg/kg/day is associated with CNS and bone toxicity; tissue loading may occur at lower doses (Federal Register, 2002). See manufacturer’s labeling.

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Other warnings/precautions:

• Resistance to treatment: May occur with depressed hematopoiesis, alcoholism, and deficiencies of other vitamins.

Pregnancy Risk Factor

A

Pregnancy Considerations

Water soluble vitamins cross the placenta. Folate requirements increase during pregnancy. Folate supplementation during the periconceptual period decreases the risk of neural tube defects (ACOG 2003; USPSTF 2009). Folate supplementation (doses larger than the RDA) is recommended for women who may become pregnant (IOM 1998). Folic acid is also indicated for the treatment of anemias due to folate deficiency in pregnant women.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber injection site pain or irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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