Ibuprofen × Methotrexate

Ibuprofen (NSAID) suppresses renal methotrexate excretion via prostaglandin-dependent renal blood flow inhibition and competition for tubular secretion. Methotrexate plasma levels rise – particularly dangerous at oncologic doses.

Mouth ulcers (mucositis), nausea, diarrhoea, hair loss. Blood counts fall: leukocytes, platelets, erythrocytes. Severe cases include fatal pancytopenia, nephrotoxicity, and hepatotoxicity.

At oncologic methotrexate doses, the combination is not prescribed. At low rheumatologic doses, short ibuprofen courses are acceptable with full blood count and creatinine monitoring. For chronic analgesia: paracetamol or celecoxib (minimal risk).