Reduces drug effectiveness
Avoid high-dose folic acid during malaria treatment.
Reduces drug levels
Monitor phenytoin levels when adding folic acid.
Reduces drug effectiveness
Avoid with cancer-dose methotrexate. USE with low-dose methotrexate.
Enhances drug toxicity
Do not supplement during fluorouracil-based chemotherapy.
L-methylfolate supplements show wild variation: 0-280% of labeled amount in one study. Folic acid is more stable and reliable.
Not Prohibited.
L-methylfolate supplements show wild variation: 0-280% of labeled amount in one study. Folic acid is more stable and reliable.
Independently graded against 178,763 indexed supplements and 757 reviewed supplement and medication pairs, sourced from PubMed, FDA CAERS, openFDA, and NIH DSLD | Last updated: April 5, 2026
Not medical advice. Based on published clinical research and systematic reviews.
Safety
Methotrexate
Your prescriber may recommend this
This medicine can lower your folate. Ask your prescriber whether you need it.
Folic acid supplementation reduces the incidence of methotrexate-induced gastrointestinal and hepatic toxicity without significantly compromising its clinical efficacy in rheumatoid arthritis.
Methotrexate is a folate antagonist that inhibits dihydrofolate reductase, leading to depletion of intracellular folate and subsequent inhibition of purine and pyrimidine synthesis. Folic acid supplementation replenishes folate stores, counteracting the toxic effects of methotrexate on healthy rapidly dividing cells.
Folic acid is routinely prescribed alongside methotrexate. In a double-blind placebo-controlled trial it did not reduce methotrexate's efficacy and lowered toxicity scores. Take it as prescribed.
DUAL ROLE: For CANCER use, folic acid may reduce methotrexate efficacy and is generally avoided unless prescribed. For RA / autoimmune use, folic acid 1 mg/day is standard of care to reduce methotrexate toxicity. Context is critical, discuss with your prescriber.
Methotrexate inhibits dihydrofolate reductase. Folic acid bypasses this inhibition.
Phenytoin (Dilantin)
Ask your prescriber first
Enzyme-inducing anti-seizure medicines lower folate and supplementation is routinely advised, especially before and during pregnancy. High-dose folic acid can lower phenytoin levels and reduce seizure control, so doses above the usual supplement range need monitoring.
ALL women of childbearing potential on antiepileptic drugs MUST take folic acid 4-5mg/day (10x standard prenatal dose). Start BEFORE conception.
AEDs deplete folate via multiple mechanisms (CYP induction, gut absorption interference). Folate deficiency multiplies neural-tube-defect risk in pregnancy.
Your prescriber may recommend this
This medicine can lower your folate. Ask your prescriber whether you need it.
Enzyme-inducing anti-seizure medicines lower folate and supplementation is routinely advised, especially before and during pregnancy. Evidence is class-level for enzyme-inducing AEDs; the phenytoin-level-lowering caveat is phenytoin-specific and omitted here.
ALL women of childbearing potential on antiepileptic drugs MUST take folic acid 4-5mg/day (10x standard prenatal dose). Start BEFORE conception.
AEDs deplete folate via multiple mechanisms (CYP induction, gut absorption interference). Folate deficiency multiplies neural-tube-defect risk in pregnancy.
5-Fluorouracil (5-FU)
Educational information only. This is not medical advice. These statements have not been evaluated by the FDA. Talk to your prescriber before starting, stopping, or combining any supplement with prescription medication.