Lansoprazole and Methotrexate Interaction

Drug interaction information between Lansoprazole and Methotrexate.

Lansoprazole and Methotrexate have a documented minor interaction in FDA labeling.

FDA drug labeling documents a minor-severity interaction between Lansoprazole 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

Lansoprazole

Proton Pump Inhibitor (PPI)

Drug B

Methotrexate

Disease-Modifying Antirheumatic Drug (DMARD)

How They Interact

Lansoprazole can prevent your body from getting rid of methotrexate quickly, which can cause the drug to build up to toxic levels.

FDA Label Information

Methotrexate Clinical Impact: Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [ see Warnings and Precautions ( 5.10 )] . Intervention : A temporary withdrawal of Lansoprazole may be considered in some patients receiving high-dose methotrexate.

Methotrexate Also Interacts With

View all Methotrexate interactions →

Frequently Asked Questions

What SPL severity band is on file for Lansoprazole + 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 Lansoprazole's 14. In the minor band specifically: Lansoprazole has 10 (also Warfarin, Ketoconazole, Itraconazole, Voriconazole); Methotrexate has 26 (also Aspirin, Folic Acid, Probenecid, Phenytoin).

What mechanism field is on file for Lansoprazole and Methotrexate?

Lansoprazole can prevent your body from getting rid of methotrexate quickly, which can cause the drug to build up to toxic levels.

Lansoprazole carries more major-labeled pairs than Methotrexate

SPL source-record counts only. This page's band is minor · classes on file: Lansoprazole (Proton Pump Inhibitor (PPI)); Methotrexate (Disease-Modifying Antirheumatic Drug (DMARD)).

Lansoprazole has 2 major-labeled pairs vs Methotrexate's 0. This page itself is in the minor band, not the major band.

Lansoprazole

2 major · 2 moderate · 10 minor · 14 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.