folic acid
Folvite

Available forms
Available by prescription only
Injection: 10-ml vials (folic acid 5 mg/ml contains 1.5% benzyl alcohol and EDTA; Folvite 5 mg/ml contains 1.5% benzyl alcohol)
Tablets: 1 mg
Tablets: 0.4 mg, 0.8 mg

Indications and dosages
 Megaloblastic or macrocytic anemia secondary to folic acid deficiency, hepatic disease, alcoholism, intestinal obstruction, excessive hemolysis. Pregnant and breast-feeding patients: 0.8 mg P.O., S.C., or I.M. daily.
Adults and children age 4 and older: 0.4 mg P.O., S.C., or I.M. daily for 4 to 5 days. After anemia secondary to folic acid deficiency is corrected, proper diet and RDA supplements are needed to prevent recurrence.
Children younger than age 4: Up to 0.3 mg P.O., S.C., or I.M. daily.
 Prevention of megaloblastic anemia of pregnancy and fetal damage. Adults: 1 mg P.O., S.C., or I.M. daily during pregnancy.
 Nutritional supplement. Adults: 0.15 to 0.2 mg P.O., S.C., or I.M. daily for men; 0.15 to 0.18 mg P.O., S.C., or I.M. daily for women.
Children: 0.05 mg P.O. daily.
 Tropical sprue. Adults: 3 to 15 mg P.O. daily.

Pharmacodynamics
Nutritional action: Exogenous folate is required to maintain normal erythropoiesis and to perform nucleoprotein synthesis. Folic acid stimulates production of RBCs, WBCs, and platelets in certain megaloblastic anemias.
Dietary folic acid is present in foods, primarily as reduced folate polyglutamate. This vitamin may be absorbed only after hydrolysis, reduction, and methylation occur in the GI tract. Conversion to active tetrahydrofolate may require vitamin B₁₂.
Oral synthetic form of folic acid is a monoglutamate and is absorbed completely after administration, even in malabsorption syndromes.

Pharmacokinetics
Absorption: Absorbed rapidly from the GI tract, mainly from the proximal part of the small intestine. Normal serum folate levels range from 0.005 to 0.015 mcg/ml. Usually, serum levels less than 0.005 mcg/ml indicate folate deficiency; those less than 0.002 mcg/ml usually result in megaloblastic anemia.
Distribution: The active tetrahydrofolic acid and its derivatives are distributed into all body tissues; the liver contains about half of the total body folate stores. Folate is actively concentrated in the CSF. Folic acid is distributed into breast milk.
Metabolism: Metabolized in the liver to N-methyltetrahydrofolic acid, the main form of folate storage and transport.
Excretion: A single 0.1-mg to 0.2-mg dose usually results in only a trace amount of drug in urine. After administering large doses, excessive folate is excreted unchanged in urine. Small amounts of folic acid have been recovered in feces. About 0.05 mg/day of normal body folate stores is lost by a combination of urinary and fecal excretion and oxidative cleavage of the molecule.

Contraindications and precautions
Contraindicated in patients with undiagnosed anemia (because it may mask pernicious anemia) and in those with pernicious anemia and other megaloblastic anemias where vitamin B₁₂ is deficient.

Interactions
Drug-drug. Aminosalicylic acid, chloramphenicol, hormonal contraceptives, methotrexate, pyrimethamine, sulfasalazine, triamterene, trimethoprim: May act as antagonists to folic acid. Monitor patient for decreased drug effect.
Anticonvulsants, such as phenobarbital and phenytoin: Increases anticonvulsant metabolism and decreases anticonvulsant levels. Monitor serum blood levels.
Phenytoin, primidone: Decreases serum folate levels; long-term therapy causes symptoms of folic acid deficiency. Monitor patient closely.
Pyrimethamine: Interferes with antimicrobial actions of pyrimethamine against toxoplasmosis. Avoid use together.

Adverse reactions
CNS: general malaise.
Respiratory: bronchospasm.
Skin: allergic reactions (rash, pruritus, erythema).

Effects on lab test results
• May decrease serum and RBC folate levels.

Overdose and treatment
Folic acid is relatively nontoxic. Adverse GI and CNS effects have been reported rarely in patients receiving 15 mg of folic acid daily for 1 month.

Special considerations
• The RDA for folic acid is 25 to 200 mcg in children and 180 to 200 mcg in adults; 100 mcg daily is considered an adequate oral supplement. Pregnant women need 400 mcg daily. During the first 6 months of breast-feeding, women need 280 mcg daily. During the second 6 months, this requirement decreases to 260 mcg daily.
• The preferred route of administration for folic acid is P.O. The manufacturer recommends deep I.M., S.C., or I.V. only when P.O. treatment isn’t feasible or when malabsorption is suspected.
• Patients undergoing renal dialysis are at risk for folate deficiency.
• Protect folic acid injections from light.
Pregnant patients
• Starting therapy before pregnancy may reduce risk of fetal neural tube defects.
Breast-feeding patients
• Folic acid appears in breast milk. Daily doses of 0.8 mg are sufficient to maintain a normoblastic bone marrow after clinical symptoms have subsided and blood components have returned to normal.

Patient education
• Advise patient of potential adverse reactions.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use