Drug Interactions Newsletter

Volume 1, Issue 13, 04/14/2009

Question

If not primarily by decreasing renal filtration, then by what mechanism does the NSAID ibuprofen (Advil®; Motrin®) increase methotrexate (Rheumatrex®; Trexall®) concentrations thereby increasing the patient's risk for myelosuppression and hepatotoxicity?

Answer

Methotrexate (Rheumatrex®; Trexall®) is a chemotherapeutic agent used as part of a treatment regimen for a number of cancers.  It is also commonly used in the chronic treatment of psoriasis and rheumatoid arthritis (RA) in doses significantly lower than those used for cancer.(1,2)  In particular, patients with rheumatoid arthritis (RA) generally have pain and inflammation of joints that warrant additional analgesics which can commonly include non-steroidal anti-inflammatory drugs (NSAIDs).  Their use may be initiated by a healthcare provider or by patients themselves since they can purchase them over-the-counter (OTC) for any pain related problems.  Of the NSAIDs available, ibuprofen is one of the most commonly purchased OTC pain relievers.  According to a survey of 4,263 people in 2002 by the National Consumer League, 83% reported using OTC analgesics in the past year, 29% reported using them daily or several times per week and 15% reported using them daily.3  In addition, of the OTC analgesics used, ibuprofen was the most common at 38% of consumers followed by acetaminophen at 33%, aspirin at 16% and naproxen at 9%.(3)  Due to the high occurrence of ibuprofen use by the general public and knowing that patients with rheumatoid arthritis commonly experience chronic pain, the concomitant use of ibuprofen and methotrexate is likely.   This is important not only for clinicians to take into consideration, but also important for patients to be aware of since there is significant risk for elevations in methotrexate which could put the patient at risk for myelosuppression, hepatotoxicity and many other adverse drug events (ADE).(4-7)  What is the mechanism by which ibuprofen increases the plasma concentration of methotrexate?......To read the full answer please LOGIN or SUBSCRIBE NOW.