Brief Answer: major drug interaction between the both Detailed Answer: Hello, There is a major drug interaction between Rabeprazole and methotrexate. Rabeprazole decreases renal excretion of methotrexate i.e Rabeprazole decreases clearance of methotrexate from the kidneys. This results in higher levels of methotrexate in the blood stream and toxicities of methotrexate accordingly. You must speak to your treating doctor about this. You can request for simple H2 blockers like Ranitidine in place of Rabeprazole. Ranitidine has no drug interaction with methotrexate. This combination may be safely consumed. Hope this helps you. Regards,

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