Methotrexate and Folic Acid Interaction
Drug interaction information between Methotrexate and Folic Acid.
Methotrexate and Folic Acid have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Methotrexate and Folic Acid. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.
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
- Celecoxib moderate
- Diflunisal moderate
- Indomethacin moderate
- Mefenamic Acid moderate
- Meloxicam moderate
Folic Acid Also Interacts With
- Dapsone Topical minor
- Infliximab minor
- Phenytoin minor
- Prenatal Multivitamin minor
Frequently Asked Questions
What SPL severity band is on file for Methotrexate + Folic Acid?
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: Methotrexate has 26 (also Aspirin, Probenecid, Phenytoin, Adalimumab); Folic Acid has 5 (also Dapsone Topical, Infliximab, Phenytoin, Prenatal Multivitamin).
What mechanism field is on file for Methotrexate and Folic Acid?
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: Methotrexate (Disease-Modifying Antirheumatic Drug (DMARD)); Folic Acid (B Vitamin (Folate) Supplement).
0 major · 12 moderate · 26 minor · 38 total
- Other minor peers for Methotrexate
- Aspirin
- Probenecid
- Phenytoin
- Adalimumab
0 major · 0 moderate · 5 minor · 5 total
- Other minor peers for Folic Acid
- Dapsone Topical
- Infliximab
- Phenytoin
- Prenatal Multivitamin
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.
Read our methodology - how this data is sourced, computed, and verified.