Major
Methotrexate × Omeprazole
Antimetabolites, folic acid analogues×Proton pump inhibitors
Mechanism
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.
Symptoms
Mouth ulcers (mucositis), nausea, diarrhoea, hair loss. Blood counts fall: leukocytes, platelets, erythrocytes. Severe cases include fatal pancytopenia, nephrotoxicity, and hepatotoxicity.
Management
At oncologic methotrexate doses, the combination is not prescribed. During methotrexate cycles, replace omeprazole with ranitidine or famotidine (H2-blockers, no BCRP effect). At low rheumatologic doses, risk is minimal; omeprazole is acceptable with full blood count monitoring.