Usage
Folic acid is a water-soluble B vitamin (B9) essential for various bodily functions, including DNA synthesis, cell division, and red blood cell formation. It’s prescribed for:
- Folic acid deficiency: Treatment and prevention of folate deficiency anemia caused by inadequate dietary intake, malabsorption, increased utilization (e.g., pregnancy, lactation, hemolytic anemia), or certain medications.
- Neural tube defects (NTDs) prophylaxis: Prevention of NTDs (e.g., spina bifida, anencephaly) in developing fetuses. It is crucial for women of childbearing age, especially during the periconceptional period (one month before conception through the first trimester).
- Methanol toxicity: As an adjunct treatment in methanol poisoning to enhance the metabolism of formic acid, a toxic metabolite of methanol.
- Methotrexate toxicity prophylaxis (off-label): To mitigate the adverse effects of methotrexate, a medication used in certain cancers and autoimmune diseases.
Pharmacological Classification: Vitamin supplement, antifolate antidote (in methanol poisoning), and chemoprotectant (in methotrexate therapy).
Mechanism of Action: Folic acid is converted to tetrahydrofolic acid, the active form of folate, which acts as a cofactor for enzymes involved in DNA synthesis, purine and pyrimidine metabolism, and amino acid interconversions. It’s crucial for cell growth and division, particularly during rapid growth periods like pregnancy and infancy.
Alternate Names
- Folate
- Vitamin B9
- Pteroylmonoglutamic acid
Brand Names: Folvite, various multivitamin preparations
How It Works
Pharmacodynamics: Folic acid supports cell division and growth by providing one-carbon units essential for synthesizing purines and thymidine, which are building blocks of DNA and RNA. It also plays a role in amino acid metabolism, including the conversion of homocysteine to methionine.
Pharmacokinetics:
- Absorption: Folic acid is readily absorbed from the jejunum, primarily via active transport at low concentrations and passive diffusion at higher doses.
- Metabolism: Folic acid is converted into its active form, tetrahydrofolic acid, in the liver and other tissues.
- Elimination: Folic acid and its metabolites are excreted primarily in the urine, with minor elimination in feces and bile.
Mode of Action: Tetrahydrofolic acid serves as a cofactor for several enzymes in one-carbon transfer reactions, essential for nucleotide biosynthesis and amino acid metabolism.
Receptor Binding/Enzyme Inhibition: Folic acid doesn’t directly bind to receptors but functions as a coenzyme. In methanol toxicity, it enhances the activity of folate-dependent enzymes to accelerate formic acid detoxification.
Elimination Pathways: Primarily renal excretion; hepatic metabolism plays a minor role.
Dosage
Standard Dosage
Adults:
- Deficiency: 1 mg orally once daily. Higher doses (up to 5 mg/day) might be necessary in severe deficiency or malabsorption.
- NTDs Prophylaxis: 400-800 mcg orally once daily. Women with a prior NTD-affected pregnancy or those taking certain antiepileptic medications might need higher doses (e.g., 4 mg/day).
- Methanol Toxicity: 50-75 mg intravenously every 4 hours for 24 hours or 1 mg/kg IV every 4 hours for 24 hours.
- Methotrexate Toxicity Prophylaxis: 1 mg orally daily, potentially increasing up to 5 mg/day if toxicity arises.
Children:
- Deficiency: Dose is determined by the prescriber based on age and severity of deficiency. Infants: 15 mcg/kg/day or 50 mcg/day IV/PO/IM/SC. Children 1-10 years: 1 mg/day IV/PO/IM/SC initially, then 0.1-0.4 mg/day.
- NTDs Prophylaxis: See pediatric guidelines.
- Methanol Toxicity: 1 mg/kg IV every 4 hours for 24 hours.
Special Cases:
- Elderly Patients: Standard adult dose, with monitoring for adverse effects.
- Patients with Renal Impairment: Dose adjustment might be necessary, particularly in dialysis patients.
- Patients with Hepatic Dysfunction: Generally, no dose adjustment is required, but monitoring is recommended.
- Patients with Comorbid Conditions: Consider individual patient factors like diabetes or cardiovascular disease when adjusting dosage.
Clinical Use Cases
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: Folic acid supplementation might be considered in critically ill patients based on folate status and risk factors for deficiency.
- Emergency Situations (e.g., Methanol poisoning): As outlined above. Folic acid should be administered for at least 24-48 hours to enhance folate-dependent metabolism of formic acid to carbon dioxide and water.
Dosage Adjustments:
Modify dosage based on renal/hepatic function, underlying medical conditions, concurrent medications, and individual patient response.
Side Effects
Common Side Effects: Generally well-tolerated at recommended doses. High doses may cause:
- Nausea
- Abdominal discomfort
- Flatulence
- Bitterness in mouth
- Sleep disturbances
- Irritability
Rare but Serious Side Effects:
- Allergic reactions (e.g., rash, itching, swelling)
- Seizures (at very high doses)
Long-Term Effects:
At very high doses and long-term use:
- Masking of Vitamin B12 deficiency
- Increased risk of certain cancers (some studies suggest, more research is needed)
Adverse Drug Reactions (ADR):
Rare but requiring immediate intervention:
- Anaphylaxis
- Severe skin reactions
Contraindications
- Hypersensitivity to folic acid.
- Undiagnosed pernicious anemia (vitamin B12 deficiency) – folic acid can mask the hematological symptoms while allowing neurological damage to progress.
Drug Interactions
- Phenytoin: Folic acid can decrease phenytoin levels, potentially leading to loss of seizure control.
- Methotrexate: Folic acid may reduce methotrexate’s efficacy in some cases.
- Sulfamethoxazole/Trimethoprim, Pyrimethamine: Folic acid can decrease the effectiveness of these antibiotics.
- Alcohol: Chronic alcohol use can impair folate absorption.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: A (generally considered safe when used as directed). Folic acid is recommended during pregnancy to prevent neural tube defects.
- Fetal Risks: No significant fetal risks associated with recommended doses.
- Drug Excretion in Breast Milk: Folic acid is excreted in breast milk, but at levels generally considered safe for infants.
Drug Profile Summary
- Mechanism of Action: Essential for DNA synthesis, cell division, and red blood cell formation.
- Side Effects: Generally well-tolerated; high doses may cause gastrointestinal issues, sleep disturbances, or irritability.
- Contraindications: Hypersensitivity, undiagnosed pernicious anemia.
- Drug Interactions: Phenytoin, methotrexate, certain antibiotics.
- Pregnancy & Breastfeeding: Recommended during pregnancy; compatible with breastfeeding.
- Dosage: Varies depending on indication and patient factors (see Dosage section).
- Monitoring Parameters: Complete blood count, reticulocyte count (in anemia), homocysteine levels (if relevant).
Popular Combinations
Often included in prenatal vitamins with other essential nutrients (e.g., iron, other B vitamins).
Precautions
- General Precautions: Assess for allergies, renal/hepatic function, and potential drug interactions.
- Specific Populations: Monitor pregnant women for adequate folate intake, especially in high-risk cases.
- Lifestyle Considerations: Advise patients on dietary sources of folate and potential interactions with alcohol.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Folic Acid?
A: The dosage varies depending on the indication. For NTDs prophylaxis, 400-800 mcg/day is recommended for women of childbearing age. For treating folic acid deficiency, 1 mg/day is typical. Pediatric dosing is determined by the prescriber.
Q2: What are the common side effects of Folic Acid?
A: Folic acid is generally well-tolerated at recommended doses. High doses can cause gastrointestinal discomfort, sleep problems, and irritability.
Q3: Can Folic Acid be taken during pregnancy?
A: Yes, folic acid is recommended during pregnancy, especially during the first trimester, to prevent neural tube defects.
Q4: How does Folic Acid prevent neural tube defects?
A: Folic acid is essential for proper closure of the neural tube during early fetal development. Adequate folate levels during the periconceptional period minimize the risk of NTDs.
Q5: Who should take Folic Acid supplements?
A: All women of childbearing age, especially those planning pregnancy or who could become pregnant, should take folic acid supplements. Individuals with folic acid deficiency or certain medical conditions (e.g., those taking methotrexate) also require supplementation.
Q6: Can Folic Acid mask Vitamin B12 deficiency?
A: Yes, folic acid can mask the hematological symptoms of vitamin B12 deficiency, allowing neurological damage to progress undetected. It’s crucial to rule out B12 deficiency before initiating folic acid treatment, particularly in patients with macrocytic anemia.
Q7: Are there any drug interactions with Folic Acid?
A: Yes, folic acid can interact with phenytoin, methotrexate, and certain antibiotics. It’s important to monitor patients for potential interactions.
Q8: What are good dietary sources of folate?
A: Leafy green vegetables, legumes, citrus fruits, fortified grains, and liver are good sources of folate.
Q9: What is the difference between folic acid and folate?
A: Folate is the naturally occurring form of vitamin B9 found in food, while folic acid is the synthetic form used in supplements and fortified foods.
Q10: Can Folic Acid be given intravenously?
A: Yes, folic acid can be administered intravenously, especially in cases of severe deficiency, malabsorption, or when oral intake is not feasible (e.g., critically ill patients, methanol toxicity).
