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Does sulfasalazine share other positive or negative effects associated with aspirin due to its salicylate component?

Medical Sciences Asked on November 17, 2021

tl;dr: The common drug sulfasalazine "…should not be used in people allergic to aspirin…" because it contains salicylate. Is it known to share other positive or negative effects associated with aspirin for the same reason?


This Biology SE answer to How did sulfasalazine become a disease-modifying treatment for rheumatoid arthritis? includes the following:

A 2016 publication by the Department of Medicine at both Imperial College Healthcare Trust, and Hammersmith Hospital (both in the UK), titled, "Rheumatoid Arthritis Treatments: A Historical Perspective", states:

"Sulfasalazine: After NSAIDs and Gold, sulfasalazine (SSZ)
is the third oldest drug class that is still available to use as a
treatment of RA. In 1938, SSZ was the first drug to be synthesized
specifically for RA
. The consensus at the time was that RA was
the result of infection
and accordingly Svartz et al developed
the DMARD, SSZ (originally known as salicylazosulfapyridin)
by combining the anti-inflammatory, salicylic acid, with the
antibacterial sulfapyridine by an azo bond
."

Also, according to a publication by the Department of Medicine at Princeton:

Sulfasalazine was synthesized almost 50 years ago specifically to treat rheumatoid arthritis. At that time bacterial infection was believed to be an important factor in pathogenesis. The linkage of sulfapyridine and salicylate with an azobond was viewed as a method of combining antibacterial and antiinflammatory actions while minimizing gastric irritation. Early therapeutic results were encouraging, but the drug was discarded as an antirheumatic agent for 30 years, until its serendipitous rediscovery. Subsequent controlled trials have confirmed its efficacy, which may be related to sulfasalazine itself or to the sulfapyridine moiety.

There is also a follow-up question: How did the “serendipitous rediscovery” of sulfasalazine as an antirheumatic agent after 30 years happen?

Question: Aspirin is recommended for some conditions and contraindicated for others. How is sulfasalazine viewed in terms of either its effectiveness as an aspirin substitute if it is already being taken for RA, or as a problem where aspirin is contraindicated? Has an aspirin equivalency dose been established for sulfasalazine?

The second quote seems to suggest that the azo bond between the two molecules was used to "minimizing gastric irritation" but aspirin’s gastric side effects may be at least partly related to its presence in the blood rather than the stomach.

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