Major
Methotrexate × Pantoprazole
Antimetabolites, folic acid analogues×Proton pump inhibitors
Mechanism
Proton pump inhibitors block the renal BCRP transporter, reducing methotrexate clearance. At high oncologic doses: risk of severe delayed 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 pantoprazole 5 days before and resume 5 days after dosing. Alternative: famotidine (H2-blocker, no BCRP effect). At low rheumatologic doses, pantoprazole is acceptable.