Rolapitant and Methotrexate Interaction
Drug interaction information between Rolapitant and Methotrexate.
Rolapitant and Methotrexate have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Rolapitant 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
Rolapitant blocks a protein that removes methotrexate from your system, which can cause the drug to build up to unsafe levels.
What To Do
Your doctor should monitor you closely for side effects since methotrexate has a narrow safety range.
FDA Label Information
BCRP Substrates with a Narrow Therapeutic Index (e.g., methotrexate, topotecan, or irinotecan) Clinical Impact: Increased plasma concentrations of BCRP substrates (e.g., methotrexate, topotecan, or irinotecan) may result in potential adverse reactions [see Clinical Pharmacology (12.3) ].
Rolapitant Also Interacts With
- Pimozide major
- Thioridazine major
- Rifampin moderate
- Rosuvastatin minor
- Warfarin minor
Methotrexate Also Interacts With
- Celecoxib moderate
- Diflunisal moderate
- Indomethacin moderate
- Mefenamic Acid moderate
- Meloxicam moderate
Frequently Asked Questions
Can I take Rolapitant and Methotrexate together?
This is a minor interaction. Your doctor should monitor you closely for side effects since methotrexate has a narrow safety range.
How serious is the interaction between Rolapitant 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 Rolapitant and Methotrexate interact?
Rolapitant blocks a protein that removes methotrexate from your system, which can cause the drug to build up to unsafe levels.
Understanding the Rolapitant and Methotrexate Interaction
FDA-approved prescribing information for these two drugs flags their combination as a minor-severity interaction. Rolapitant belongs to the NK1 Receptor Antagonist (Antiemetic) 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: Rolapitant blocks a protein that removes methotrexate from your system, which can cause the drug to build up to unsafe levels. 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. Rolapitant has 9 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 should monitor you closely for side effects since methotrexate has a narrow safety range. 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 Rolapitant 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.