FOLIC ACID: 22,864 Adverse Event Reports & Safety Profile

Folic acid, N-[ p -[[(2-amino-4- hydroxy-6-pteridinyl) methyl]- amino] benzoyl]-L glutamic acid, is a B complex vitamin containing a pteridine moiety linked by a methylene bridge to para -aminobenzoic acid, which is joined by a peptide linkage to glutamic acid. Conjugates of folic acid are present in a wide variety of foods, particularly liver, kidneys, yeast, and leafy green vegetables. Commercially available folic acid is prepared synthetically. Folic acid, USP occurs as a yellow or yellowish-orange crystalline powder and is very slightly soluble in water and insoluble in alcohol. Folic acid, USP is readily soluble in dilute solutions of alkali hydroxides and carbonates, and solutions of the drug may be prepared with the aid of sodium hydroxide or sodium carbonate, thereby forming the soluble sodium salt of folic acid (sodium folate). Aqueous solutions of folic acid are heat sensitive and rapidly decompose in the presence of light and/or riboflavin; solutions should be stored in a cool place protected from light. The structural formula of folic acid is as follows: C 19 H 19 N 7 O 6 M.W.

441.40 Each 1 mL of solution, for oral administration, contains 0.2 mg folic acid, USP. QUIOFIC ® (folic acid)

Oral

Solution, 0.2 mg/mL contains the following inactive ingredients: edetate disodium, methylparaben, mixed berry flavor, propylene glycol, propylparaben, purified water, sodium phosphate dibasic, sodium phosphate monobasic, and sorbitol solution.

Chemical

Structure

Helps restore and maintain natural vaginal moisture levels, supporting comfort during menopause. Supports natural hydration and helps maintain the elasticity of vaginal tissues. Assists in relieving vaginal dryness, discomfort, itching, and sensitivity caused by hormonal changes. Designed to support the natural balance of the vaginal microbiome and mucosa.

AND ADMINISTRATION Recommended starting dosage in adults and pediatric patients (regardless of age) is up to 1 mg orally daily. ( 2 ) Maintenance dosage ( 2 ) - Pediatric patients birth to 23 months: 0.1 mg orally daily - Pediatric patients 2 years to less than 4 years: up to 0.3 mg orally daily - Adults and pediatric patients 4 years and older: 0.4 mg orally daily - Pregnant and Lactating Women: 0.8 mg orally daily; but never less than 0.1 mg orally per day

2.1 Important Administration Information Instruct patients or caregivers to use an oral dosing syringe to correctly measure the prescribed amount of medication. Inform patients that oral dosing syringes may be obtained from their pharmacy.

2.2 Recommended Dosing Initial Dosing The recommended starting dosage of FOLIC ACID oral solution in pediatric and adult patients is up to 1 mg orally daily. FOLIC ACID oral solution can be taken with or without food. Rule out pernicious anemia prior to use of any doses greater than 0.4 mg (except during pregnancy and lactation).

Maintenance Dosing

When clinical symptoms have subsided and the blood picture has become normal, use a daily maintenance level as follows: - Pediatric patients aged birth to 23 months: 0.1 mg orally daily - Pediatric patients aged 2 years to less than 4 years: up to 0.3 mg orally daily - Pediatric patients aged 4 years and older and adult patients: 0.4 mg orally daily - Pregnant and Lactating Women: 0.8 mg orally daily; but never less than 0.1 mg orally per day Higher maintenance doses may be needed in the presence of alcoholism, hemolytic anemia, anticonvulsant therapy, or chronic infection. Monitor patients frequently for relapse and adjust dose accordingly.

FOLIC ACID oral solution is contraindicated in patients with a history of a hypersensitivity reaction to folic acid or any of the ingredients of QUIOFIC [see Description (11) ]. FOLIC ACID oral solution is contraindicated in patients with a history of a hypersensitivity reaction to folic acid or any of the ingredients of QUIOFIC. ( 4 )

ADVERSE REACTIONS Allergic sensitization has been reported following both oral and parenteral administration of folic acid. Folic acid is relatively nontoxic in man. Rare instances of allergic responses to folic acid preparations have been reported and have included erythema, skin rash, itching, general malaise, and respiratory difficulty due to bronchospasm. One patient experienced symptoms suggesting anaphylaxis following injection of the drug. Gastrointestinal side effects, including anorexia, nausea, abdominal distention, flatulence, and a bitter or bad taste, have been reported in patients receiving 15 mg folic acid daily for 1 month. Other side effects reported in patients receiving 15 mg daily include altered sleep patterns, difficulty in concentrating, irritability, overactivity, excitement, mental depression, confusion, and impaired judgment. Decreased vitamin B 12 serum levels may occur in patients receiving prolonged folic acid therapy. In an uncontrolled study, orally administered folic acid was reported to increase the incidence of seizures in some epileptic patients receiving phenobarbital, primidone, or diphenylhydantoin. Another investigator reported decreased diphenylhydantoin serum levels in folate-deficient patients receiving diphenylhydantoin who were treated with 5 mg or 15 mg of folic acid daily. CALL YOUR DOCTOR FOR MEDICAL ADVICE ABOUT SIDE EFFECTS. YOU MAY REPORT SIDE EFFECTS TO THE FDA AT 1-800-FDA-1088 OR LEADING PHARMA, LLC AT 1-844-740-7500.

AND PRECAUTIONS Folic acid in doses above 0.1 mg daily may obscure pernicious anemia in that hematologic remission can occur while neurologic manifestations remain progressive. This may result in severe nervous system damage before the correct diagnosis is made. ( 5.1 )

5.1 Risk of Obscuring Diagnosis of Pernicious Anemia The use of single-agent FOLIC ACID oral solution (without the use of vitamin B12) is not recommended for the treatment of pernicious anemia and other megaloblastic anemias in which vitamin B 12 is deficient. Folic acid in doses above 0.1 mg daily may obscure pernicious anemia in that hematologic remission can occur while neurologic manifestations remain progressive. There is a potential danger in administering folic acid to patients with undiagnosed anemia, since folic acid may obscure the diagnosis of pernicious anemia by alleviating the hematologic manifestations of the disease while allowing the neurologic complications to progress. This may result in severe nervous system damage before the correct diagnosis is made. Adequate doses of vitamin B 12 may prevent, halt, or improve the neurologic changes caused by pernicious anemia.

PRECAUTIONS General Folic acid in doses above 0.1 mg daily may obscure pernicious anemia in that hematologic remission can occur while neurologic manifestations remain progressive. There is a potential danger in administering folic acid to patients with undiagnosed anemia, since folic acid may obscure the diagnosis of pernicious anemia by alleviating the hematologic manifestations of the disease while allowing the neurologic complications to progress. This may result in severe nervous system dam age before the correct diagnosis is made. Adequate doses of vitamin B 12 may prevent, halt, or improve the neurologic changes caused by pernicious anemia.

Drug Interactions

There is evidence that the anticonvulsant action of phenytoin is antagonized by folic acid. A patient whose epilepsy is completely controlled by phenytoin may require increased doses to prevent convulsions if folic acid is given. Folate deficiency may result from increased loss of folate, as in renal dialysis and/or interference with metabolism (e.g., folic acid antagonists such as methotrexate); the administration of anticonvulsants, such as diphenylhydantoin, primidone, and barbiturates; alcohol consumption and, especially, alcoholic cirrhosis; and the administration of pyrimethamine and nitrofurantoin. False low serum and red cell folate levels may occur if the patient has been taking antibiotics, such as tetracycline, which suppress the growth of Lactobacillus casei. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals to evaluate carcinogenic potential and studies to evaluate the mutagenic potential or effect on fertility have not been con ducted.

Pregnancy Teratogenic Effects Pregnancy

Category A Folic acid is usually indicated in the treatment of megaloblastic anemias of pregnancy. Folic acid requirements are markedly increased during pregnancy, and deficiency will result in fetal damage (see INDICATIONS AND USAGE). Studies in pregnant women have not shown that folic acid increases the risk of fetal abnormalities if administered during pregnancy. If the drug is used during pregnancy, the possibility of fetal harm appears remote. Because studies cannot rule out the possibility of harm, however, folic acid should be used during pregnancy only if clearly needed.

Nursing Mothers

Folic acid is excreted in the milk of lactating mothers. During lactation, folic acid requirements are markedly increased; however, amounts present in human milk are adequate to fulfill infant requirements, although supplementation may be needed in low- birth-weight infants, in those who are breast-fed by mothers with folic acid deficiency (50 mcg daily), or in those with infections or prolonged diarrhea.

INTERACTIONS Anticonvulsant action of phenytoin is antagonized by folic acid. ( 7 ) Multiple drug classes, including anticonvulsants, antibiotic/antimicrobial agents, folate antagonists, GI-binding agents, and oral contraceptives, may reduce folic acid absorption or folate levels. ( 7 )

7.1 Impact of Folic Acid on Other Drugs Folic acid may interfere with gastrointestinal absorption of methotrexate. Folic acid therapy in folate-deficient individuals may decrease serum levels of phenytoin. Folic acid may also interfere with the absorption and effectiveness of antibiotic tetracycline. Folic acid supplements are usually avoided on the day of oral methotrexate administration. Generally, the time of administration of these drugs should be separated from folic acid.

7.2 Impact of Other Drugs on Folic Acid A wide range of medications can affect folic acid levels through multiple mechanisms, including impaired absorption, accelerated metabolism, and direct inhibition of folate pathways. Enzyme-inducing anticonvulsants such as phenytoin, primidone, carbamazepine, phenobarbital, and the broader anticonvulsant class increase hepatic folate metabolism, inhibit intestinal folate-processing enzymes, raise gastrointestinal pH, or displace folate from serum proteins, collectively leading to decreased folate availability. Valproate and sulfasalazine primarily reduce intestinal folate absorption or interfere with folate-dependent metabolic pathways, while isoniazid and cycloserine reduce folate utilization through metabolic disruption. Several antifolate agents, including trimethoprim, pyrimethamine, methotrexate, and triamterene, directly inhibit dihydrofolate reductase, decreasing the formation of active folate derivatives. Additional agents such as pentamidine, antacids, cholestyramine, colestipol, and H 2 blockers impair gastrointestinal folate uptake through pH elevation, transporter inhibition, or binding of dietary folate. Nitrous oxide indirectly decreases folate activity by inactivating vitamin B12 and downstream methylation pathways, while oral contraceptives increase folate turnover and urinary loss. While on FOLIC ACID oral solution treatment, if patients are concomitantly using any of the drugs or drug classes mentioned above, then monitor for reduced efficacy and adjust the dose of FOLIC ACID oral solution as needed.

Acidum folicum 4X HPUS – Contributes to the regeneration and repair of vaginal tissues. Acidum lacticum 2X HPUS – Helps regulate vaginal pH and supports microbiome balance.

Extractum

Salviae officinalis 3X HPUS – Helps reduce irritation and supports hydration.

Oleum

Melaleucae alternifolia (Tea Tree Oil) 4X HPUS – Traditionally used in homeopathy to support the body’s natural defenses against external imbalances, helping to protect and maintain a healthy vaginal microbiome.

Soybean Extract, PEG 32, Lactosum, Polysorbate 20, PEG 20, Proteose Pepton, Natrii Chloridum, Sodium Hyaluronate