Rabeprazole and Methotrexate Interaction
Drug interaction information between Rabeprazole and Methotrexate.
Rabeprazole and Methotrexate have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Rabeprazole and Methotrexate. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.
How They Interact
Rabeprazole can keep methotrexate in your body longer than usual, which might lead to dangerous levels of the drug in your blood.
What To Do
Your doctor might have you stop taking rabeprazole for a short time if you are receiving high doses of methotrexate.
FDA Label Information
Methotrexate Clinical Impact: Concomitant use of rabeprazole with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of methotrexate with PPIs have been conducted [see Warnings and Precautions ( 5.9 )]. Intervention: A temporary withdrawal of rabeprazole sodium delayed-release tablets may be considered in some patients receiving high dose methotrexate administration.
Rabeprazole Also Interacts With
- Amoxicillin major
- Clarithromycin major
- Warfarin minor
- Ketoconazole minor
- Itraconazole minor
Methotrexate Also Interacts With
- Celecoxib moderate
- Diflunisal moderate
- Indomethacin moderate
- Mefenamic Acid moderate
- Meloxicam moderate
Frequently Asked Questions
Can I take Rabeprazole and Methotrexate together?
This is a minor interaction. Your doctor might have you stop taking rabeprazole for a short time if you are receiving high doses of methotrexate.
How serious is the interaction between Rabeprazole and Methotrexate?
This interaction is classified as "minor" severity by the FDA. Minor interactions are unlikely to cause significant problems but should still be mentioned to your healthcare provider.
Why do Rabeprazole and Methotrexate interact?
Rabeprazole can keep methotrexate in your body longer than usual, which might lead to dangerous levels of the drug in your blood.
Understanding the Rabeprazole and Methotrexate Interaction
FDA-approved prescribing information for these two drugs flags their combination as a minor-severity interaction. Rabeprazole belongs to the Proton Pump Inhibitor (PPI) class and Methotrexate belongs to the Disease-Modifying Antirheumatic Drug (DMARD) class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Rabeprazole can keep methotrexate in your body longer than usual, which might lead to dangerous levels of the drug in your blood. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.
Context around a specific patient determines real-world impact. Rabeprazole has 7 total documented interactions on file in this dataset, and Methotrexate has 38. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: Your doctor might have you stop taking rabeprazole for a short time if you are receiving high doses of methotrexate. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.
An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Rabeprazole or Methotrexate based on a web page, speak with your prescriber or pharmacist before making any change.
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.
Read our methodology - how this data is sourced, computed, and verified.