Folic Acid and Methotrexate Interaction

Drug interaction information between Folic Acid and Methotrexate.

Folic Acid and Methotrexate have a documented minor interaction in FDA labeling.

FDA drug labeling documents a minor-severity interaction between Folic Acid and Methotrexate. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.

Drug A

Folic Acid

B Vitamin (Folate) Supplement

Drug B

Methotrexate

Disease-Modifying Antirheumatic Drug (DMARD)

How They Interact

Folic acid can interfere with how methotrexate works to treat cancer, making the medication less effective.

FDA Label Information

Folic Acid Coadministration of methotrexate with folic acid or its derivatives decreases the clinical effectiveness of methotrexate in patients with neoplastic diseases.

Methotrexate Also Interacts With

View all Methotrexate interactions →

Frequently Asked Questions

What SPL severity band is on file for Folic Acid + Methotrexate?

Compiled FDA labeling labels this pair minor. That is a source-record field, not an individual medication-combination decision.

Which drug in this pair has the larger labeled-interaction portfolio?

Methotrexate has 38 labeled pairs on file vs Folic Acid's 5. In the minor band specifically: Folic Acid has 5 (also Dapsone Topical, Infliximab, Phenytoin, Prenatal Multivitamin); Methotrexate has 26 (also Aspirin, Probenecid, Phenytoin, Adalimumab).

What mechanism field is on file for Folic Acid and Methotrexate?

Folic acid can interfere with how methotrexate works to treat cancer, making the medication less effective.

Methotrexate's labeled portfolio outnumbers Folic Acid

SPL source-record counts only. This page's band is minor · classes on file: Folic Acid (B Vitamin (Folate) Supplement); Methotrexate (Disease-Modifying Antirheumatic Drug (DMARD)).

Folic Acid

0 major · 0 moderate · 5 minor · 5 total

Methotrexate

0 major · 12 moderate · 26 minor · 38 total

Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. This registry does not provide individual medication-combination directions.