Major
Amoxicillin × Methotrexate
Penicillins with extended spectrum×Antimetabolites, folic acid analogues
Mechanism
Amoxicillin and other penicillins compete with methotrexate for renal tubular secretion. Methotrexate clearance falls and plasma levels rise – risk of myelosuppression and toxicity at oncologic doses.
Symptoms
Mouth ulcers (mucositis), nausea, diarrhoea, hair loss. Blood counts fall: leukocytes, platelets, erythrocytes. Severe cases: fatal pancytopenia, nephrotoxicity.
Management
At oncologic methotrexate doses, avoid amoxicillin. Alternative antibiotics: a cephalosporin or macrolide (azithromycin, doxycycline). At low rheumatologic doses, a short amoxicillin course is acceptable with blood count monitoring.