Methotrexate × Omeprazole

Omeprazole blocks the renal BCRP transporter and reduces methotrexate clearance. At oncologic methotrexate doses, plasma levels rise 2- to 3-fold, with reported severe nephrotoxicity and pancytopenia.

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

With high-dose (oncology) methotrexate, the Spanish label requires avoiding proton pump inhibitors, especially in renal impairment. Withhold omeprazole for the course and use an H2-receptor antagonist such as famotidine for gastric protection. Ranitidine is not an option: it has been suspended in the EU since 2020. With low-dose methotrexate (rheumatology, psoriasis) the combination is possible, but the labels warn about methotrexate accumulation, so monitor blood counts, creatinine and signs of toxicity such as mouth ulcers and diarrhoea, with extra care in reduced kidney function.