renal toxicity

methotrexate + nsaids

Methotrexate is cleared almost entirely by the kidneys. NSAIDs reduce renal blood flow by blocking prostaglandins and compete with methotrexate at renal tubular transporters, both of which slow methotrexate elimination and raise its blood levels. The danger is greatest with high-dose methotrexate (cancer chemotherapy) or pre-existing kidney impairment, where the buildup can cause bone marrow suppression, mouth and gut ulceration, liver injury, and acute kidney injury. In low-dose weekly methotrexate for autoimmune disease with healthy kidneys, the interaction is usually more modest and often manageable under prescriber supervision.