Moderate
Azithromycin × Methotrexate
Macrolides×Antimetabolites, folic acid analogues
Mechanism
Antibiotics may affect methotrexate gut absorption. Low clinical significance at rheumatological methotrexate doses (5–25 mg weekly).
Symptoms
Mostly no changes. At high oncologic methotrexate doses: risk of rising levels with toxicity symptoms (stomatitis, diarrhoea, falling leukocyte count).
Management
At low rheumatological methotrexate doses, the combination is acceptable without adjustment. At high oncologic doses: avoid azithromycin; alternative antibiotics (a cephalosporin, nitrofurantoin for UTI).