Probenecid markedly increases
serum methotrexate levels (3- to 4-fold).
A marked increase in both the therapeutic and toxic effects of
methotrexate can occur, apparently even with low doses if other risk factors are present (e.g.
renal impairment, concurrent NSAIDs). Anticipate the need to reduce the dosage of the
methotrexate and monitor the effects well if
probenecid is also taken. If this is not possible, avoid the combination.