Acetylsalicylic acid × Methotrexate

Aspirin suppresses tubular secretion of methotrexate and displaces it from albumin binding. Methotrexate plasma levels rise – particularly dangerous at oncologic doses.

Mouth ulcers (mucositis), nausea, diarrhoea, hair loss. Blood counts fall: leukocytes, platelets, erythrocytes. Severe cases include fatal pancytopenia, nephrotoxicity, and hepatotoxicity.

Aspirin SmPCs, including those for 100 mg products, contraindicate aspirin during methotrexate treatment at 15 mg a week or more (aspirin 100 mg and 500 mg SmPCs). Below 15 mg a week the interaction still has to be taken into account, especially with impaired kidney function; if the combination is needed, monitor full blood count and kidney function, particularly in the first days (aspirin SmPCs). The methotrexate SmPC for rheumatological use allows NSAIDs and salicylates to continue with low-dose methotrexate only under strict medical supervision; with any kidney impairment, even mild, NSAIDs are not recommended, and while they are taken blood counts and kidney function are checked more often than the usual schedule (methotrexate 2.5 mg SmPC). With high oncological methotrexate doses, NSAIDs are not given before or together with methotrexate (methotrexate 100 mg/ml SmPC). If the combination cannot be avoided, the FDA advises close monitoring for methotrexate adverse reactions (US methotrexate label).