Drug Interactions Newsletter

Volume 1, Issue 38, 10/06/2009

Question

What is the mechanism by which naproxen (Aleve®; Anaprox®; Anaprox DS®; Naprosyn®) can increase the serum concentrations of methotrexate (Rheumatrex®; Trexall®) and risk for significant side effects such as bone marrow suppression or hepatotoxicity?

Answer

The concomitant use of methotrexate and naproxen is plausible especially in patients with rheumatoid arthritis (RA) where pain is commonly treated by patients themselves or clinicians with the use of non-steroidal antiinflammatory drugs (NSAIDs).  The current Food and Drug Administration (FDA) approved product package inserts (PI) for both methotrexate dosage formulations, Rheumatrex® and Trexall®, have specific warnings regarding the coadministration of NSAIDs and methotrexate.  If used together there are risks for unexpectedly severe (and sometimes fatal) bone marrow suppression, aplastic anemia and/or gastrointestinal toxicity.(1,2)  The PIs recommend a dose reduction of methotrexate when NSAIDs are used concurrently.(1,2)  This is based, in part, on case reports showing severe....

The complete answer to this question also comes with a figure that outlines the mechanism for this drug interaction.