Folic acid (folate) and Methotrexate interaction

Folic acid (folate) and Methotrexate: the Methotrexate prescribing label describe an interaction that usually calls for monitoring, a dose change, or spacing the doses.

Moderate

Usually manageable with monitoring or a dose change. Tell your pharmacist you take both.

What the FDA labels say

From the Methotrexate (Xatmep) label · effective 2026-05-28

Moderate

Nitrous Oxide The use of nitrous oxide anesthesia potentiates the effect of methotrexate on folate-dependent metabolic pathways, resulting in the potential for increase toxicity.

Drug interactionsnames Folic acid (folate)View label on DailyMed

Curated guidance for Folic acid (folate)

Moderate

Methotrexate is a folate antagonist; folic acid is often prescribed with it to reduce side effects, but high doses can reduce its anticancer effect.

Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.