Major
Ibuprofen × Methotrexate
Non-steroidal anti-inflammatory drugs (NSAIDs)×Antimetabolites, folic acid analogues
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.