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Concomitant therapy with NSAIDS and/or salicylates results in elevated and prolonged serum Methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity.
Methotrexate is partially bound to serum albumin and toxicity may be increased due to displacement by salicylates, phenylbutazone, phenytoin and sulfonamides. Allopurinol may increase the incidence of cytotoxic induced bone marrow depression.
