Folic acid (vitamin B9) is used to treat megaloblastic anaemias due to folate deficiency, including anaemias of nutritional origin, pregnancy, infancy and childhood, and those associated with coeliac disease. It is an essential vitamin for blood cell formation. Supplementation of 0.4 mg/day is recommended in pregnancy to prevent neural tube defects.
Also known as: folato, folate, vitamina B9, vitamin B9
The combination is generally safe with no relevant interaction; usual therapy can be maintained.
Folic acid and ciprofloxacin do not share pharmacokinetic or pharmacodynamic pathways that would justify a clinically relevant interaction. There is no evidence that ciprofloxacin alters folate levels or that folic acid interferes with the antibacterial activity of the fluoroquinolone. The combination is common in practice (for example, prophylaxis in immunocompromised patients) and can be maintained without adjustments, only respecting the usual schedules of each drug.
The combination is generally safe with no relevant interaction; usual therapy can be maintained.
No known interaction mechanism between folate and fluoroquinolones.
No specific additional monitoring.
No specific red flags.
No dose adjustment needed.
DailyMed (FDA) — approved Folic acid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0baa10dd-6d1d-4946-8236-566451132da3 ; approved Ciprofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c527d138-e32c-418f-9573-a3d8a796279f — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Sulfasalazine may reduce folic acid absorption and its effect, especially with long-term use.
The sulfasalazine label documents that "reduced absorption of folic acid and digoxin have been reported when these agents were administered concomitantly with sulfasalazine" and that "sulfasalazine inhibits the absorption and metabolism of folic acid, which may interfere with folic acid supplementation". The mechanism involves sulfapyridine (a sulfasalazine metabolite) which inhibits the reduced folate carrier (RFC) intestinal transporter. This interaction is particularly relevant in women of childbearing age with IBD (risk of neural tube defects) and in patients with megaloblastic anaemia or high-dose sulfasalazine. Supplement with folic acid 1 mg/day (or 5 mg if planning pregnancy) and monitor serum folate levels, haemoglobin and MCV; consider divided doses of sulfasalazine to minimise sulfapyridine exposure.
Folic acid + sulfasalazine: sulfasalazine reduces intestinal folate absorption (sulfapyridine). Supplement and monitor folate levels.
Inhibition of the intestinal folate transporter by sulfapyridine (a sulfasalazine metabolite).
Monitor blood count and signs of megaloblastic anaemia.
Megaloblastic anaemia.
Consider folic acid supplementation in patients on long-term therapy, especially with anaemia or pregnancy.
DailyMed (FDA) — approved Sulfasalazine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d967092f-9685-446b-b7b8-17821e29417b ; approved Folic acid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0baa10dd-6d1d-4946-8236-566451132da3 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Chronic alcohol use interferes with folate metabolism and absorption, potentially worsening deficiency.
Limit alcohol intake during folic acid treatment.
EMC-UK (MHRA) — approved Folic acid SmPC: https://www.medicines.org.uk/emc/product/6998/smpc
Folic acid may correct macrocytosis and mask an undiagnosed vitamin B12 deficiency.
Rule out B12 deficiency before starting folic acid in patients with macrocytic anaemia.
EMC-UK (MHRA) — approved Folic acid SmPC: https://www.medicines.org.uk/emc/product/6998/smpc
Folic acid is recommended before and during pregnancy to prevent neural tube defects.
Supplement 400-800 µg/day preconception and in the 1st trimester (higher doses at high risk).
Excreted into breast milk; safe during breastfeeding.
No specific additional contraception.
EMC-UK (MHRA) — approved Folic acid SmPC: https://www.medicines.org.uk/emc/product/6998/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Water-soluble vitamin (folate) essential for nucleoprotein synthesis and the maintenance of normal erythropoiesis. It corrects megaloblastic anaemias due to folate deficiency (nutritional, pregnancy, infancy, tropical/non-tropical sprue). Normal serum folate ranges from 5 to 15 ng/mL; levels below 2 ng/mL usually result in megaloblastic anaemia. Relatively non-toxic; adverse effects are rare (allergic reactions, GI upset at 15 mg/day).
Folic acid is the precursor of tetrahydrofolic acid, which acts as a cofactor in transformylation reactions in the biosynthesis of purines and thymidylates of nucleic acids. Impaired thymidylate synthesis accounts for the defective DNA synthesis that leads to megaloblast formation and megaloblastic/macrocytic anaemias. Its action on megaloblastic marrow produces a normoblastic marrow.
Rapidly absorbed from the small intestine, primarily from the proximal portion. It appears in plasma approximately 15 to 30 minutes after an oral dose; peak levels are generally reached within 1 hour. Naturally occurring conjugated folates are reduced enzymatically to folic acid in the GI tract prior to absorption. CSF folate levels are several times greater than serum levels.
Metabolised in the liver to 7,8-dihydrofolic acid and then to 5,6,7,8-tetrahydrofolic acid (with the aid of DPNH and folate reductases); tetrahydrofolate derivatives are distributed to all body tissues but stored mainly in the liver. After a single 15 mg oral dose, up to 90% of the dose is recovered in the urine; excretion is generally complete within 24 hours. Small amounts are recovered in faeces and folate is also excreted in breast milk.
No classical plasma elimination half-life: after low doses (100 mcg) only a trace amount appears in urine, whereas doses of 5 mg or 40 mcg/kg result in about 50% of the dose in urine and 15 mg in up to 90% (majority in the first 6 hours, excretion complete within 24 hours). Normal erythrocyte folate levels range from 175 to 316 ng/mL.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
