Major
Established
描述
NSAIDs reduce methotrexate renal elimination, raising its plasma levels and significantly increasing the risk of methotrexate toxicity (myelosuppression, mucositis, nephrotoxicity).
机制
NSAIDs reduce renal blood flow via prostaglandin inhibition and compete with methotrexate for renal tubular secretion, reducing its clearance and prolonging exposure.
临床意义
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.
处理措施
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.