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.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.