methotrexate and amoxicillin

Amoxicillin reduces renal tubular secretion of methotrexate, likely by inhibiting the organic anion transporter (OAT) in the proximal tubule. This decreases methotrexate clearance and raises its plasma concentration.

Elevated methotrexate levels can cause severe toxicity, including bone marrow suppression (pancytopenia), mucositis, hepatotoxicity, and renal failure. Reports of fatal outcomes exist, particularly with high-dose methotrexate.

Avoid concurrent use if possible. If unavoidable, use with caution and monitor serum methotrexate concentrations, full blood count, and renal function. Consider reducing the methotrexate dose and providing appropriate rescue with folinic acid. An alternative antibiotic should be considered in high-dose methotrexate regimens.

Interaction is well documented in case reports and pharmacokinetic studies, especially with penicillins. Guidelines recommend caution with high-dose methotrexate.