MajorNon-steroidal anti-inflammatory drugs (NSAIDs)×Antimetabolites, folic acid analogues
Updated · Methodology
Mechanism
Ibuprofen reduces methotrexate renal elimination by inhibiting proximal tubular secretion. With high-dose methotrexate (oncology, high-dose psoriasis) concentration rises 2–3 fold causing severe myelosuppression and mucositis. With low-dose weekly methotrexate (rheumatoid arthritis 7.5–25 mg/week) risk is lower but not absent.
Symptoms
Within 7–14 days: mouth ulcers, fever, infections, bruising, gum bleeding. CBC: leukopenia, thrombocytopenia; rising creatinine.
Management
With high-dose methotrexate, contraindicated: stop NSAID 48 h before infusion, resume no sooner than 2–3 days after. With low-dose weekly methotrexate, choose paracetamol as first-line analgesic. If an NSAID is needed, check CBC, creatinine and transaminases every 2 weeks for the first 2 months.
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
- EULAR: EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological DMARDs (2022)– Ann Rheum Dis 2023;82:3-18
- FDA: Methotrexate Sodium Tablets prescribing information (2016)– ; DailyMed setid 8f1260de-b60c-4f0e-8af6-0e957b0a281b
- AEMPS: Ficha técnica: Ibuprofeno (nº registro 63597), sección 4.5 (2025)– AEMPS, CIMA, nº registro 63597, revisión 04/2025, sección 4.5