synthetic DMARD, is metabolized to sulfapyri-dine and 5-aminosalicylic acid.
The sulfapyridine is probably the active moiety when treating rheumatoid
arthritis (unlike inflam-matory bowel disease). Some authorities believe that
the parent compound, sulfasalazine, also has an effect. In treated arthritis
patients, IgA and IgM rheumatoid factor produc-tion are decreased. Suppression
of T-cell responses to concanavalin and inhibition of in vitro B-cell
proliferation have also been docu-mented. In vitro, sulfasalazine or its
metabolites inhibit the release of inflammatory cytokines, including those
produced by mono-cytes or macrophages, eg, interleukins-1, -6, and -12, and
These findings suggest a possible mechanism for the clinical efficacy of
sulfasalazine in rheumatoid arthritis.
Only 10–20% of orally
administered sulfasalazine is absorbed, although a fraction undergoes
enterohepatic recirculation into the bowel where it is reduced by intestinal
bacteria to liberate sulfapyridine and 5-aminosalicylic acid (see Figure 62–8).
Sulfapyridine is well absorbed while 5-aminosalicylic acid remains unabsorbed.
Some sulfasalazine is excreted unchanged in the urine whereas sulfapyridine is
excreted after hepatic acetylation and hydroxylation. Sulfasalazine’s half-life
is 6–17 hours.
effective in rheumatoid arthritis and reduces radio-logic disease progression.
It has also been used in juvenile chronic arthritis and in ankylosing
spondylitis and its associated uveitis. The usual regimen is 2–3 g/d.
Approximately 30% of
patients using sulfasalazine discontinue the drug because of toxicity. Common
adverse effects include nausea, vomiting, headache, and rash. Hemolytic anemia
and methemo-globinemia also occur, but rarely. Neutropenia occurs in 1–5% of
patients, while thrombocytopenia is very rare. Pulmonary toxicity and positive
double-stranded DNA (dsDNA) are occasionally seen, but drug-induced lupus is
rare. Reversible infertility occurs in men, but sulfasalazine does not affect
fertility in women. The drug does not appear to be teratogenic.