Misoprostol and Methotrexate Interaction

Drug interaction information between Misoprostol and Methotrexate.

Misoprostol and Methotrexate have a documented moderate interaction in FDA labeling.

FDA drug labeling documents a moderate-severity interaction between Misoprostol 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

Misoprostol

Prostaglandin E1 Analog

Drug B

Methotrexate

Disease-Modifying Antirheumatic Drug (DMARD)

How They Interact

The diclofenac in this medicine can stop your body from getting rid of methotrexate properly. This can cause methotrexate to build up to harmful levels in your blood.

FDA Label Information

Methotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Intervention: During concomitant use of diclofenac sodium/misoprostol and methotrexate, monitor patients for methotrexate toxicity.

Methotrexate Also Interacts With

View all Methotrexate interactions →

Frequently Asked Questions

What SPL severity band is on file for Misoprostol + Methotrexate?

Compiled FDA labeling labels this pair moderate. 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 Misoprostol's 12. In the moderate band specifically: Misoprostol has 3 (also Diclofenac, Diflunisal); Methotrexate has 12 (also Celecoxib, Diflunisal, Indomethacin, Mefenamic Acid).

What mechanism field is on file for Misoprostol and Methotrexate?

The diclofenac in this medicine can stop your body from getting rid of methotrexate properly. This can cause methotrexate to build up to harmful levels in your blood.

Methotrexate's labeled portfolio outnumbers Misoprostol

SPL source-record counts only. This page's band is moderate · classes on file: Misoprostol (Prostaglandin E1 Analog); Methotrexate (Disease-Modifying Antirheumatic Drug (DMARD)).

Misoprostol

0 major · 3 moderate · 9 minor · 12 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.