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4.2 Therapeutic dosage Folic acid should never be given alone or in conjunction with
inadequate amounts of Vitamin B12 for the treatment of
4.2.1 Adults undiagnosed megaloblastic anaemia. Although folic acid may
produce a haematopoietic response in patients with
Folate deficient megoblastic anaemia megaloblastic anaemia due to Vitamin B12, it fails to prevent
the onset of subacute combined degeneration of the cord
Therapeutic dose (Reynolds, 1989).
5 mg daily orally for 4 months; up to 15 mg daily may
be required in malabsorption states.(UK) 5. ROUTES OF ENTRY
Following oral administration of single 0.1 to 0.2 mg doses Adverse gastrointestinal and central nervous
of folic acid in health adults, only a trace amount of the system effects have been reported rarely in
drug appears in urine . Following administration of large patients receiving 15 mg of folic acid daily
doses, the renal tubular reabsorption maximum is exceeded, for one month. However, other studies have
excess folate is excreted unchanged in urine. Small amounts failed to confirm these findings (McEvoy,
of orally administered folic acid have been recovered from 1990).
faeces. About 0.05 mg/day of normal body folate stores is
lost by a combination of urinary and faecal excretion and 7.2.1.2 Children
oxidative cleavage of the molecule. No data available.
7. PHARMACOLOGY AND TOXICOLOGY Folic acid therapy may increase phenytoin metabolism in
folate deficient patients resulting in decreased phenytoin
7.1 Mode of action serum concentration. It has also been reported that
concurrent administration of folic acid and chloramphenicol
7.1.1 Toxicodynamics in folate deficient patients may result in antagonism of the
haematopoietic response to folic acid.
Folic acid is relatively non-toxic. Toxicity studies in
mice showed that folic acid could cause convulsions, The use of ethotoin or mephenytoin concurrently with folic
acid may decrease the effects of hydantoins by increasing 10. MANAGEMENT
hydantoin metabolism.
10.1 General principles
Trimethoprim acts as a folate antagonist by inhibiting
dihydrofolate reductase, so in patients receiving this drug In cases of overdose, treatment is symptomatic and
leucovorin calcium must be given instead of folic acid. Folic supportive and is guided by the clinical features.
acid may also interfere with the effects of pyrimethamine.
In case of anaphylactic reaction standard treatment should
Aminopterin (4 aminofolic acid) and methotrexate (4 amino- 10 be given. (See Treatment Guide on Anaphylaxis).
methylfolic acid) antagonizes reduction of folic acid to
tetrahydrofolic acid. Methotrexate continues to be used as an In case of massive ingestion gastric lavage or induced
antineoplastic drug whose activity may be dependent on vomiting could be considered if seen within 1 to 2 hours
blocking certain syntheses, e.g., of purines, in which folic after ingestion. Activated charcoal should be given
acid is required, thereby depriving neoplastic cells of repeatedly in view of the enterohepatic circulation of
compounds essential for their proliferation. Calcium folic acid.
leucovorin is used therapeutically as a potent antidote for
the toxic effects of folic acid antagonists used as 10.3 Life supportive procedures and symptomatic/specific
antineoplastic agents. Methotrexate or pyrimethamine or treatment
triamterene also acts as folate antagonist by inhibiting
dihydrofolic reductase (USP DI, 1983). Treatment is largely supportive. In case of anaphylactic
reaction, epinephrine (adrenaline) should be given.
Analgesics, anticonvulsants, antimalarials and Maintain a clear airway and aspirate secretions from
corticosteroids may cause folic acid deficiency (USP DI, airway. Administer oxygen and perform endotracheal
1983). intubation when necessary. Support ventilation using
appropriate mechanical device. Control convulsions with
Folic acid precipitates in some proprietary amino acid appropriate drug regimen. Perform cardio-respiratory
solutions and in the presence of high concentration of resuscitation when necessary. Correct hypotension with
calcium ions, but it appears to be stable and remains in isotonic fluids and inotropic agents.
solution provided the pH remains above 5. There have also
been reports of folic acid being absorbed by the polyvinyl 10.4 Decontamination
chloride containers and administration set, however, other
studies have not substantiated such observations. In case of massive ingestion induce vomiting or gastric
lavage, if seen within 1 to 2 hours after ingestion.
Regarding intravenous incompatibilities, calcium gluconate Repeat dose activated charcoal.
and folic acid injections have been shown to interact even
though a precipitate is not present. The recoverable amount 10.5 Elimination
of folic acid from a 10 mg/ml solution declined with
increasing concentrations (0.5 to 10 mg/ml) of calcium Adequate hydration would be sufficient to eliminate the
gluconate. This interaction was reversed by the addition of drug through the kidneys.
edetic acid (Trissel, 1986).
10.7 Management discussion
7.7 Main adverse effects
Folic acid is relatively non-toxic and management is
Allergic reactions to folic acid have been rarely reported directed toward symptomatic and supportive therapy.
including erythema, rash, itching, general malaise and
bronchospasm. Adverse gastrointestinal and central nervous The only allergic reaction to folic acid, which is life
system effects have been reported in patients receiving 15 mg threatening, is anaphylaxis. For anaphylaxis one should
of folic acid daily for one month. give epinephrine (adrenaline) and (if considered necessary)
corticosteroids and fluids.
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
For hypotension unresponsive to volume expansion, one may
8.1 Sample give dopamine.