Major
Esomeprazole × Methotrexate
Drugs for peptic ulcer and GORD. Proton pump inhibitors×Antimetabolites, folic acid analogues
Mechanism
Proton pump inhibitors block the renal BCRP transporter and reduce methotrexate clearance. At high oncologic doses, risk of delayed elimination and severe toxicity.
Symptoms
Mouth ulcers (mucositis), nausea, diarrhoea, hair loss. Blood counts fall: leukocytes, platelets, erythrocytes. Severe cases: fatal pancytopenia, nephrotoxicity.
Management
At oncologic methotrexate doses, stop esomeprazole 5 days before and resume 5 days after dosing. Alternative: famotidine (H2-blocker, no BCRP effect). At low rheumatologic doses, esomeprazole is acceptable with blood count monitoring.