methotrexate and aspirin

Aspirin reduces the renal clearance of methotrexate by inhibiting renal prostaglandin synthesis and by competing for tubular secretion. It may also displace methotrexate from plasma protein binding, increasing free plasma concentrations.

Concomitant use can lead to elevated methotrexate concentrations, increasing the risk of severe toxicity including myelosuppression, mucositis, hepatotoxicity, nephrotoxicity, and potentially fatal outcomes.

Avoid concurrent use if possible. If combination is necessary, use a lower methotrexate dose, monitor plasma methotrexate concentrations, renal function, and full blood count closely, and adjust therapy accordingly.

Well-established interaction documented in numerous pharmacokinetic studies and clinical reports. The risk is particularly high in patients with impaired renal function or when high-dose methotrexate is used.