Nonsteroidal anti-inflammatory drugs with methotrexate

El-Sheikh AA, van den Heuvel JJ, Koenderink JB, et al. Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport. J Pharmacol Exp Ther 2007 320 229-235. 

Concomitant use of heparin and oral anticoagulants can increase the risk for bleeding due to the antiplatelet effect of aspirin. In addition, use with alcohol can increase the risk of Gl bleeding. / spirin displaces a number of drugs (e.g., tolbutamide, nonsteroidal anti-inflammatory drugs [NSAIDs], methotrexate, phenytoin, and probenecid) from protein binding sites in the blood. Corticosteroid use can reduce serum salicylate levels by increasing the clearance of aspirin. 

At this stage, an assessment is made as to whether the medicine that could result is likely to be palliative or disease-modifying . Diseasemodifying drugs (DMD) are those which directly and beneficially deflect the natural history of the disease. Nonsteroidal anti-inflammatory drugs and methotrexate are examples of each of these in patients with rheumatoid arthritis. Then probability of one or the other can alter economic assessments of the research program, and lead to a go-no-go decision in some cases. 

Drug interactions may potentiate methotrexate toxicity. For example nonsteroidal anti-inflammatory drugs can reduce renal clearance of methotrexate, resulting in toxic levels. Table 96-5 lists selected drugs that interact with, and increase toxicity of, methotrexate. 

Although there have been many reports describing how patients with EMS have been treated, results were not successful in the majority of patients. Basically, the treatment of EMS has consisted of discontinuation of L-tryp-tophan and administration of corticosteroids, nonsteroidal anti-inflammatory drugs, and several other drugs, such as D-penicillamine and colchicine, cyclophosphamide, AZA (azathioprine), methotrexate, amitriptyline, acetaminophen, aspirin, naproxen, diphenhydramine, cyclobenzaprine, and fluoxetine.2132 56 In general, it was concluded that prednisone was helpful in the acute phase of the disease. Slow improvement was reported in 79% of the 193 patients. However, no treatment was clearly valuable in the management of the later phase of the syndrome.55... 

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