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Sulfasalazine: Pharmacology, administration, and adverse effects in the treatment of rheumatoid arthritis

Michael H Weisman, MD
Renee Z Rinaldi, MD
Section Editor
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Deputy Editor
Paul L Romain, MD


Salicylazosulfapyridine (sulfasalazine, SSZ) is a nonbiologic (conventional or traditional) disease-modifying antirheumatic drug (DMARD) that was originally proposed as a treatment for rheumatoid arthritis (RA) because of its antiinflammatory and antimicrobial activities [1,2]. It has also been used for other inflammatory joint disorders and for inflammatory bowel disease (IBD).

Initial studies in the 1940s suggested a beneficial effect in patients with RA, but the drug's efficacy was challenged by the findings of a negative, small, open-label 1949 report, which was influential despite a flawed study design [3,4]. Additionally, the introduction of cortisone during this period, an event then hailed as a modern medical miracle, further dampened enthusiasm for the use of SSZ in RA. However, a resurgence of interest in SSZ as a therapeutic agent for rheumatic disorders occurred after beneficial results were reported in a trial performed in the late 1970s and in the first placebo-controlled trial in 1983, and it is widely available [5,6].

The pharmacology, dosing, and adverse effects of SSZ as used in the treatment of RA and other forms of inflammatory arthritis are discussed here. The use and relative efficacy of SSZ in the management of RA and other conditions are presented separately. (See "General principles of management of rheumatoid arthritis in adults" and "Alternatives to methotrexate for the initial treatment of rheumatoid arthritis in adults" and "Treatment of rheumatoid arthritis in adults resistant to initial nonbiologic DMARD therapy" and "Treatment of arthritis associated with inflammatory bowel disease", section on 'Management of peripheral arthritis' and "Treatment of peripheral spondyloarthritis", section on 'Resistant to initial therapy' and "Sulfasalazine and 5-aminosalicylates in the treatment of inflammatory bowel disease".)


Sulfasalazine (SSZ) is a prodrug composed of 5-aminosalicylic acid (5-ASA) linked to sulfapyridine through an azo bond (figure 1). Approximately 30 percent of orally administered SSZ, which therapeutically is a relatively inactive chemical, is rapidly absorbed by the small bowel and is then returned, largely unaltered, via the enterohepatic circulation into the bile. Thus, approximately 90 percent of the ingested drug reaches the large intestine as an intact molecule [3,7].

In the colon, SSZ is reduced by the bacterial enzyme azoreductase to its two components, sulfapyridine and 5-ASA. Thus, coliform bacteria are necessary to reduce the relatively inactive parent drug to its active moieties. Nearly all of the sulfapyridine is absorbed, while 5-ASA is largely excreted in the feces, consistent with the utility of 5-ASA in inflammatory bowel disease (IBD).

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Literature review current through: Nov 2017. | This topic last updated: Oct 12, 2017.
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