Methotrexate in combination with NSAIDs or coxibs

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" Caution should be used when NSAIDs are administered concurrently with lower

doses of methotrexate. In patients with rheumatoid arthritis, methotrexate

has been given concurrently with NSAIDs without apparent problems. It should

be noted that the doses of methotrexate used in rheumatoid arthritis are

lower than those used in psoriasis or malignant disease; these higher doses

may lead to unexpected toxicity in combination with NSAIDs. In general,

NSAID therapy can decrease the clearance of methotrexate, resulting in

elevated and prolonged serum methotrexate levels. The potential for an

interaction between methotrexate and celecoxib or rofecoxib has not been

evaluated in large trials; patients should be monitored closely for signs of

methotrexate toxicity while receiving these combinations. In a small

pharmacokinetic study, methotrexate pharmacokinetics were not affected by

celecoxib in arthritis patients receiving maintenance doses of methotrexate.

Rofecoxib has been reported to decrease methotrexate clearance in one small

study. Concurrent use of NSAIDs may lead to an increased risk of GI bleeding

in patients with methotrexate-induced thrombocytopenia. "

Source:

http://www.cai.mcgill.ca/meded/DrugDB/methotrexate/methotrexate_db.htm

" Rofecoxib 75 mg administered once daily for 10 days increased plasma

concentrations by 23% as measured by AUC0-24 hr in patients receiving

methotrexate 7.5 to 15 mg/week for rheumatoid arthritis. An equivalent

magnitude of reduction in methotrexate renal clearance was observed. At 24

hours postdose, a similar proportion of patients treated with methotrexate

alone (94%) and subsequently treated with methotrexate co-administered with

75 mg of rofecoxib (88%) had methotrexate plasma concentrations below the

measurable limit (5 ng/ml). The effects of the recommended doses for

osteoarthritis (12.5 and 25 mg) of rofecoxib on plasma methotrexate levels

are unknown. Standard monitoring of methotrexate-related toxicity should be

continued if rofecoxib and methotrexate are administered concomitantly. "

Source: http://www.genrx.com/genrxfree/Top_200_2000/Drugs/E3435.htm

Note: Rofecoxib = Vioxx