%0 Journal Article
%T Interactions among Low Dose of Methotrexate and Drugs Used in the Treatment of Rheumatoid Arthritis
%A Marinella Patan¨¨
%A Miriam Ciriaco
%A Serafina Chimirri
%A Francesco Ursini
%A Saverio Naty
%A Rosa Daniela Grembiale
%A Luca Gallelli
%A Giovambattista De Sarro
%A Emilio Russo
%J Advances in Pharmacological Sciences
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/313858
%X Methotrexate (MTX) is a nonbiological disease-modifying antirheumatic drug that has shown both a good control of clinical disease and a good safety. Usually drug-drug interactions (DDIs) represent the most limiting factor during the clinical management of any disease, in particular when several drugs are coadministered to treat the same disease. In this paper, we report the interactions among MTX and the other drugs commonly used in the management of rheumatoid arthritis. Using Medline, PubMed, Embase, Cochrane libraries, and Reference lists, we searched for the articles published until June 30, 2012, and we reported the most common DDIs between MTX and antirheumatic drugs. In particular, clinically relevant DDIs have been described during the treatment with MTX and NSAIDs, for example, diclofenac, indomethacin, or COX-2 inhibitors, and between MTX and prednisone or immunosuppressant drugs (e.g., leflunomide and cyclosporine). Finally, an increase in the risk of infections has been recorded during the combination treatment with MTX plus antitumor necrosis factor-¦Á agents. In conclusion, during the treatment with MTX, DDIs play an important role in both the development of ADRs and therapeutic failure. 1. Introduction Rheumatoid arthritis (RA) is a chronic and autoimmune disease affecting about 1% of people, with the highest incidence between 40 and 70 years [1]. Drugs able to reduce inflammation and cells activation may be used in the management of RA. In particular, nonsteroidal anti-inflammatory drugs (NSAIDs) as well as immunosuppressive agents (i.e., glucocorticoids), disease-modifying antirheumatic drugs (DMARDs), and agents that are able to block the proinflammatory cytokine tumor necrosis factor-¦Á (anti-TNF-¦Á) may be used (Table 1). Table 1: Drugs used in the management of rheumatoid arthritis. NSAIDs, acting on cyclooxygenases, are able to control the inflammation and the clinical symptoms [2¨C4], but not the disease¡¯s progression; their use as monotherapy for a long time is limited for the development of adverse drug reactions (ADRs) [5]. Glucocorticoids (e.g., dexamethasone and prednisone) are anti-inflammatory and immune suppressor agents that are able to reduce the inflammation and the progression of RA, through the inhibition of cytokines secretion and osteoclasts activation [6¨C15]. However, even if they represent a first-line treatment in patients with RA, their use is limited for the development of serious ADRs such as loss of bone mass, increased risk of fractures, infections, diabetes and hypertension [16¨C18]. The DMARDs group, includes
%U http://www.hindawi.com/journals/aps/2013/313858/