Folic acid is vitamin B9, essential for making red blood cells and for the baby’s development in pregnancy. Deficiency causes anaemia; in pregnant women, it prevents serious neural tube defects.
Also known as: Folato, Vitamina B9
Folic acid increases phenytoin metabolism, lowering serum concentrations of the antiepileptic and possibly increasing seizure frequency.
Increased phenytoin metabolism by folate: the Prontuário (Folic acid 4.1.2) states that "folic acid may increase phenytoin metabolism with reduced serum concentrations of the antiepileptic and a possible increase in seizure frequency".
Serum phenytoin levels, seizure frequency, full blood count and folate/B12.
Increased seizure frequency or severity, status epilepticus.
Maintain supplementation when indicated (for example in pregnancy) but monitor phenytoin levels and seizure control, adjusting the antiepileptic dose; do not change dosing without monitoring.
INFARMED Prontuário Terapêutico (11th ed., 2012), Folic acid 4.1.2 — phenytoin metabolism and seizure risk.
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)
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)
Synthetic folic acid is well absorbed with or without food; food does not interfere clinically.
Take with or without food, at the same time (site monograph).
Site monograph (folic acid — pregnancy dose 400–800 mcg/day, started before conception).
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
Before folate alone in macrocytic anaemia, ALWAYS exclude B12 deficiency (subacute combined degeneration risk).
Measure B12 before starting folate alone (site monograph).
Site monograph (folic acid — exclude B12 deficiency before folate alone).
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
No restriction — on the contrary: folic acid supplementation (400–500 µg/day) is recommended for ALL women planning pregnancy and in the 1st trimester to prevent neural tube defects. Annex 1 cites 5 mg/day doses when haemolysis is induced (dapsone) or on antiepileptic treatment. At very high doses (>>5 mg) it can mask B12 deficiency.
Compatible and recommended in all trimesters at the standard dose; 5 mg/day in risk situations (antiepileptics, haemolysis, deficiency).
Compatible; folate passes into milk and is essential to the infant.
No specific additional contraception.
Prontuário Terapêutico INFARMED — Annex 1 l. 39907 ("administer 5 mg/day folic acid to the mother" with dapsone); 11.3.2. WHO periconceptional folic acid guidance.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Correction of macrocytic anaemia and prevention of neural tube defects; homocysteine reduction.
Reduced to tetrahydrofolate (THF) and intracellularly polyglutamated; THF donates one-carbon units for purine and thymidylate synthesis (dTMP → DNA).
Duodenal absorption via PCFT transporter; oral bioavailability ~ 85%, higher than food folate.
Hepatic hydrolysis to THF; renal excretion (free folate and metabolites).
~ 3 h (folate pool distribution); haematological effect visible in 5–7 days.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
