Major
Established
Description
Ibuprofen reduces methotrexate clearance and can cause severe methotrexate toxicity including life-threatening bone marrow suppression.
Mechanism
Ibuprofen inhibits renal prostaglandin synthesis, reducing renal blood flow and tubular secretion of methotrexate; it also competes for organic anion transporters involved in methotrexate excretion.
Clinical Significance
Fatal cases of methotrexate toxicity have been reported when NSAIDs were used concurrently; even low-dose MTX regimens carry risk.
Management
Avoid combination; monitor CBC, renal function, and MTX levels closely if unavoidable. Withhold ibuprofen for 48 h before and after MTX dose.