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.
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.