FOLIC ACID

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: M.W. 441.40 Each 1 mL of solution, for oral administration, contains 0.2 mg folic acid, USP. 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

FOLIC ACID oral solution is indicated for the treatment of megaloblastic anemias due to folic acid deficiency in adult and pediatric patients. FOLIC ACID oral solution is a folate analog indicated for the treatment of megaloblastic anemias due to folic acid deficiency in adult and pediatric patients. ( 1 )

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 )

The following clinically significant adverse reactions are described elsewhere in the labeling: Risk of Obscuring Diagnosis of Pernicious Anemia [see Warnings and Precautions (5.1) ] The following adverse reactions associated with the use of folic acid were identified in clinical studies or post marketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Adverse Reactions: Hypersensitivity reactions including rash, itching, malaise, and bronchospasm. Gastrointestinal reactions (nausea, anorexia, abdominal distension, flatulence, dysgeusia) Neurological reactions (altered sleep patterns, difficulty concentrating, irritability, overactivity, excitement, depression, confusion, impaired judgement) Decreased vitamin B 12 serum levels (with prolonged folic acid therapy). Increased seizures in patients with epilepsy receiving phenobarbital, primidone, or diphenylhydantoin The most common adverse reactions are nausea, anorexia, and bloating. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Ayurax, LLC at 1-844-551-9911 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.