methotrexate and diclofenac

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

Concurrent use can lead to elevated methotrexate concentrations, increasing the risk of severe toxicity, including myelosuppression, mucositis, hepatotoxicity, and renal failure. Fatal outcomes have been reported.

Avoid co-prescription if possible. If necessary, use with extreme caution: monitor renal function, blood counts, and methotrexate levels frequently; consider a lower methotrexate dose and ensure adequate hydration and alkalinisation.

Well-established interaction with multiple case reports and pharmacokinetic studies. Caution advised in guidelines for methotrexate prescribing.