Major
Established
Descrição
NSAIDs reduce methotrexate renal elimination, raising its plasma levels and significantly increasing the risk of methotrexate toxicity (myelosuppression, mucositis, nephrotoxicity).
Mecanismo
NSAIDs reduce renal blood flow via prostaglandin inhibition and compete with methotrexate for renal tubular secretion, reducing its clearance and prolonging exposure.
Significância Clínica
Methotrexate AUC can increase 2–4-fold; severe and fatal toxicity (pancytopenia, acute renal failure) has been reported, especially at higher methotrexate doses used for oncology.
Conduta
Avoid high-dose methotrexate + NSAIDs; low-dose rheumatology regimens require caution—monitor CBC, renal function, and methotrexate levels. Withhold NSAID for 24–48 h around weekly methotrexate dose if possible.