MajorNon-steroidal anti-inflammatory drugs (NSAIDs)×Antimetabolites, folic acid analogues
Updated · Methodology
Mechanism
Diclofenac, like other NSAIDs, reduces methotrexate renal clearance. With high-dose methotrexate – fatal myelosuppression and nephrotoxicity. With low-dose methotrexate – higher risk of cytopenia and liver injury.
Symptoms
Same as with ibuprofen: mucositis, cytopenia, rising creatinine and transaminases.
Management
Same approach as methotrexate+ibuprofen. If a rheumatoid arthritis patient needs an NSAID, prefer paracetamol or a short ibuprofen course with lab monitoring.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Sources
- FDA: Methotrexate Sodium Tablets prescribing information (2016)– ; DailyMed setid 8f1260de-b60c-4f0e-8af6-0e957b0a281b
- DailyMed: Methotrexate: FDA prescribing information, Drug Interactions section (DailyMed) (2024)
- AEMPS: Ficha técnica: Diclofenaco (nº registro 62161), sección 4.5 (2025)– AEMPS, CIMA, nº registro 62161, revisión 08/2025, sección 4.5