Methotrexate and Misoprostol Interaction

Drug interaction information between Methotrexate and Misoprostol.

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

FDA drug labeling documents a moderate-severity interaction between Methotrexate and Misoprostol. 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

Methotrexate

Disease-Modifying Antirheumatic Drug (DMARD)

Drug B

Misoprostol

Prostaglandin E1 Analog

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 Methotrexate + Misoprostol?

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: Methotrexate has 12 (also Celecoxib, Diflunisal, Indomethacin, Mefenamic Acid); Misoprostol has 3 (also Diclofenac, Diflunisal).

What mechanism field is on file for Methotrexate and Misoprostol?

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: Methotrexate (Disease-Modifying Antirheumatic Drug (DMARD)); Misoprostol (Prostaglandin E1 Analog).

Methotrexate

0 major · 12 moderate · 26 minor · 38 total

Misoprostol

0 major · 3 moderate · 9 minor · 12 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.