A patient with chronic myeloid leukemia on high-dose methotrexate develops severe methotrexate toxicity after being prescribed an NSAID for joint pain. Which NSAID most commonly causes this interaction, and what is the mechanism?

• A Aspirin; displacement of methotrexate from plasma protein binding sites
• B Ibuprofen; inhibition of renal tubular secretion of methotrexate via OAT transporters ✓
• C Celecoxib; inhibition of CYP2C9-mediated methotrexate metabolism
• D Diclofenac; reduced renal perfusion via prostaglandin inhibition

Explanation

Ibuprofen and other NSAIDs inhibit renal organic anion transporters (OAT1/OAT3) responsible for active tubular secretion of methotrexate, reducing its clearance and causing severe myelosuppression and mucositis. This is a well-documented drug interaction. Although NSAIDs also reduce renal prostaglandins, the primary mechanism for methotrexate toxicity is inhibition of its renal tubular secretion.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.