Folic Acid (Folate) or vitamin B 9 is an essential vitamin that is required for nucleic acid synthesis, erythropoiesis, and as a cofactor for methanol toxicity. It is recommended in pregnant women for organogenesis and to reduce the incidence of neural tube defects (spina bifida).

Folic Acid (Folate) Uses:

• Megaloblastic and macrocytic anemias due to folate deficiency:

  • It is indicated for the treatment of megaloblastic anemia due to folate deficiency.

• Off Label Use of Folic Acid in Adults:

  • As an alternative to leucovorin calcium (calcium folinate), it may be used as an adjunctive cofactor therapy in methanol toxicity.
  • It is indicated in pregnant women at high risk of giving birth to babies with neural tube defects
  • It may be used as a supplement to reduce toxicity associated with antifolate chemotherapy.

Folic Acid (Folate) Dose in Adults

Folic Acid (Folate) Dose in the treatment of Megaloblastic and macrocytic anemias due to folate deficiency:

• 1 to 5 mg orally once a day.
• Doses up to 15 mg once a day may be given in severe cases.

• Manufacturer's labeling:

  • Oral, IM, IV, SubQ: Initial:
    • 0.4 to 1 mg/day.
  • Maintenance dose:
    • 4 mg/day
• Pregnant and lactating women:
  • Maintenance dose of 0.8 mg/day

Folic Acid (Folate) Dose in the treatment of Methanol poisoning (off-label):

• 50 to 70 mg intravenous every four hours or
• 50 mg orally every 3 to 4 hours.
• Folic acid treatment should continue until the complete elimination of methanol and formic acid.
• It should never be used as monotherapy. Cofactors are adjunctive to antidotal therapy.

Folic Acid (Folate) Dose in the Prevention of neural tube defects (off-label):

• Females of childbearing potential:

  • 4 mg/day orally daily or
  • 0.4 to 0.8 mg/day.
  • Folate supplementation should be initiated at least one month prior to conception and continue until at least 12 weeks of gestation.

• Females at high risk, those with a family history of neural tube defects, or those who have had a previous pregnancy with a neural tube defect:

  • 4 mg/day orally.
  • Folic acid supplementation should be initiated at least 3 months before conception and continued until at least the 12 weeks of gestation.

Folic Acid (Folate) Dose as Supplementation to reduce toxicity associated with antifolate chemotherapy (off-label): 

• To reduce toxicity associated with pemetrexed:

  • Give folic acid 0.35 to 1 mg once a day. Initiate folic acid treatment 1 to 3 weeks before initiating pemetrexed treatment.
  • Continue for three weeks after the last dose of pemetrexed.
  • Administer folic acid with intramuscular cyanocobalamin supplementation.

• To reduce toxicity associated with pralatrexate:

  • Give folic acid 1 to 1.25 mg once a day.
  • Beginning folate supplementation at least 10 days before initiating pralatrexate treatment.
  • The treatment must be continued for 30 days after the last pralatrexate dose.
  • It should be administered with intramuscular cyanocobalamin supplementation.

Folic Acid (Folate) Dose in Childrens

Adequate intake (AI) of Folic Acid (Folate): 

• 1-6 months:

  • 65 mcg/day

• 7-12 months:

  • 80 mcg/day

Recommended daily allowance (RDA) of Folic Acid (Folate):

• 1-3 years:

  • 150 mcg/day

• 4-8 years:

  • 200 mcg/day

• 9-13 years:

  • 300 mcg/day

• Adolescents ≥14 years:

  • 400 mcg/day

Folic Acid (Folate) Dose in the treatment of Anemia (folic acid deficiency):

Oral, IM, IV, SubQ:

• Infants:

  • 1 mg/day

• Children <4 years:

  • Up to 0.3 mg/day

• Children >4 years and Adolescents:

  • 4 mg/day

Folic Acid (Folate) Dose in the maintenance requirement of folic acid as Parenteral nutrition:

Intravenous administration:

• Infants:

  • 56 mcg/kg/day

• Children and Adolescents younger than 13 years:

  • 140 mcg/day

• Adolescents older than 13 years:

  • 400 mcg/day

Folic Acid (Folate) Dose in the prevention of Gingival hyperplasia due to phenytoin:

• Children ≥6 years and Adolescents:

  • 5 mg/day orally.

Folic Acid (Folate) use in Pregnancy (Pregnancy Risk Category: A)

• Folic Acid (Folate), a water-soluble vitamin, can cross the placental boundary. Pregnancy is when maternal needs increase.
• Folic acid is a preventive measure that reduces the risk of neural tube defects (spina bifida).
• Folate supplementation should be started before any female patient plans to get pregnant.
• Spina-bifida is a condition in which a woman's risk of having a baby with a neural tube defect (spina bifida), should be taken at higher doses.
• Folate supplementation is required for pregnant women with folate deficiency.

Folic acid use during breastfeeding:

• Folic Acid (Folate), which is found in human breastmilk, is an essential nutrient. Breastfeeding women have a higher daily intake.
• Except faor severe deficiencies, maternal concentrations are not affected.

Folic Acid (Folate) Dose in Kidney Disease:

Dose adjustment in not recommended in patients with kidney disease.

Folic Acid (Folate) Dose in Liver disease:

Dose adjustment is not recommended in patients with liver disease.

Side effects of Folic Acid (Folate):

• Cardiovascular:

  • Flushing (slight)

• Central nervous system:

  • Malaise (general)

• Dermatologic:

  • Erythema
  • Pruritus
  • Skin rash

• Hypersensitivity:

  • Hypersensitivity reaction

• Respiratory:

  • Bronchospasm

Contraindications to Folic Acid (Folate):

Allergy reactions to folic acids or any other component of the formulation

Warnings and precautions

• Monotherapy for Anemia

  • Patients with pernicious anemia, aplastic anemia, and normocytic encephalopathy should avoid it as a monotherapy.

• Pernicious anemia:

  • While irreversible nerve damage is possible, doses exceeding 0.1 mg/day can obscure the symptoms of pernicious Anemia.

Folic acid: Drug Interaction

Monitoring parameters:

• Monitor for rising blood counts in patients with folate deficiency anemias.
• Observe for neurological signs if administered to patients with macrocytic anemia.
• Avoid folate administration in patients with vitamin B12 deficiency as it may worsen the neurological features associated with vitamin B12 deficiency.

How to administer Folic Acid (Folate)?

• It should preferably be administered per oral.
• However, it can also be administered by a deep Intramuscular injection, SubQ, and intravenous injections.

Intravenous administration:

• Doses 5 mg or less may be administered undiluted over greater than one minute
• It may be administered after dilution in 50 ml NS or 5% DW and infused over 30 minutes.
• Dilution is recommended for doses greater than 5 mg.
• It may also be added to intravenous solutions and given as an intravenous infusion.

Mechanism of action of Folic Acid (Folate):

• Folic acid is essential for many co-enzymes involved in metabolic pathways. 
• Folic acid is essential for the synthesis and use of pyrimidine and purines, as well as nucleoproteins and erythropoiesis.
• Folate deficiency patients also benefit from the stimulation of platelets, WBCs and other metabolic processes.
• Folic acid is helpful in the conversion of toxic metabolites of methanol (formic acids) to non-toxic substances in methanol poisoning.

The onset of action:

• Peak effect is seen when administered Orally: 0.5 to 1 hour

Absorption:

• It is absorbed in the proximal part of the small intestine

Metabolism:

• Hepatic

Bioavailability of oral folate:

• Folic acid supplement: about 100%
• In the presence of food: 85%
• Dietary folate: 50%

Time to peak serum concentration after oral administration:

• One hour

Excretion:

• Urine

International Brands of Folic Acid (Folate):

• FA-8
• JAMP-Folic Acid
• NOVO-Folacid
• SANDOZ Folic Acid
• F. Valdecasas
• Acfol
• Acide Folique CCD
• Acido Folico
• Acido Folico Fada
• Acifol
• Anemolat
• Apo-Folic
• Bio-Folic
• Clonfolic
• Conacid
• Elvefocal
• Endofolin
• Enhansid
• Feri
• Filicine
• Fionat
• Folac
• Folacid
• Folacin
• Folart
• Folate
• Folavit
• Folbiol
• Folcid
• Folee-1
• Foli 5
• Foliage
• Foliamin
• Folic Acid DHA
• Folic Acid Pharm Ecologist
• Folicap
• Folicid
• Folicil
• Folicum
• Folimax
• Folimen
• Folimet
• Folin
• Folina
• Folinsyre ”Dak”
• Foliphar
• Folitab
• Folivit
• Folivita
• Folivital
• Foloicare
• Folsan
• Folsyre
• Folverlan
• Folvit
• Folvite
• Gravi-Fol
• Gravida
• Huma-Folacid
• Ingafol
• Lexpec
• Megafol
• Mithra Folic
• Nufolic
• Obstetra
• Prinac AC
• Quatro
• RubieFol
• Tecnovorin
• Tesha-1
• Tifol
• Tonixan
• Travital Folic Acid
• Vifolin

Folic acid (Folate) Brand Names in Pakistan: