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Advances in Pharmacological Sciences
Volume 2013, Article ID 313858, 8 pages
Review Article

Interactions among Low Dose of Methotrexate and Drugs Used in the Treatment of Rheumatoid Arthritis

1Department of Health Science, School of Medicine, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
2Pharmacovigilance's Center Regione Calabria, University Hospital Mater Domini, 88100 Catanzaro, Italy
3Rheumatology Research Unit and Ph.D. Program in Molecular Oncology, Experimental Immunology and Development of Innovative Therapies, University of Catanzaro, 88100 Catanzaro, Italy

Received 17 March 2013; Revised 9 April 2013; Accepted 16 April 2013

Academic Editor: Raymond M. Quock

Copyright © 2013 Marinella Patanè et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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-α agents. In conclusion, during the treatment with MTX, DDIs play an important role in both the development of ADRs and therapeutic failure.